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The Impact of Heat Stress On The Immune System in Dairy Cattle A Review PDF
The Impact of Heat Stress On The Immune System in Dairy Cattle A Review PDF
The impact of heat stress on the immune system in dairy cattle: A review T
a a a a b c,d a,⁎
M. Bagath , G. Krishnan , C. Devaraj , V.P. Rashamol , P. Pragna , A.M. Lees , V. Sejian
a
ICAR-National Institute of Animal Nutrition and Physiology, Adugodi, Bangalore 560030, Karnataka, India
b
School of Agriculture and Food, Faculty of Veterinary and Agricultural Sciences Dookie Campus, Dookie College, The University of Melbourne, Victoria 3647 Australia
c
The University of Queensland, School of Agriculture and Food Sciences, Animal Science Group, Gatton, QLD 4343, Australia
d
University of New England, School of Environmental and Rural Science, Armidale, NSW 2350, Australia
A R T I C LE I N FO A B S T R A C T
Keywords: Heat stress is well documented to have a negative influence on livestock productivity and these impacts may be
Cell mediated immunity exacerbated by climate change. Dairy cattle can be more vulnerable to the negative effects of heat stress as these
Climate change adverse impacts may be more profound during pregnancy and lactation. New emerging diseases are usually
Cortisol linked to a positive relationship with climate change and the survival of microrganisms and/or their vectors.
Dairy cattle
These diseases may exaggerate the immune suppression associated with the immune suppressive effect of heat
Heat stress
Humoral immunity
stress that is mediated by the hypothalamic-pituitary-adrenal (HPA) and the sympathetic-adrenal–medullary
Nutrition (SAM) axes. It has been established that heat stress has a negative impact on the immune system via cell
mediated and humoral immune responses. Heat stress activates the HPA axis and increases peripheral levels of
glucocorticoids subsequently suppressing the synthesis and release of cytokines. Heat stress has been reported to
induce increased blood cortisol concentrations which have been shown to inhibit the production of cytokines
such as interleukin-4 (IL-4), IL-5, IL-6, IL-12, interferon γ (IFNγ), and tumor necrosis factor-α (TNF- α). The
impact of heat stress on the immune responses of dairy cows could be mediated by developing appropriate
amelioration strategies through nutritional interventions and cooling management. In addition, improving
current animal selection methods and the development of climate resilient breeds may support the sustainability
of livestock production systems into the future.
⁎
Corresponding author.
E-mail address: drsejian@gmail.com (V. Sejian).
https://doi.org/10.1016/j.rvsc.2019.08.011
Received 17 March 2019; Received in revised form 1 July 2019; Accepted 2 August 2019
0034-5288/ © 2019 Elsevier Ltd. All rights reserved.
M. Bagath, et al. Research in Veterinary Science 126 (2019) 94–102
from each other, they interact in a well-coordinated approach to re- 2002; Lacetera et al., 2005). Heat stress impairs the cellular immune
move and protect the body from pathogens and/or foreign substances. response by increasing the cortisol concentrations, which binds to DNA
The adaptive immune system can be further divided into Cell-Mediated inhibiting the expression of genes involved in T-cell activation and
Immunity (CMI) and Humoral Immunity (HI). T-lymphocytes are ac- cytokine production (Caroprese et al., 2012; Sgorlon et al., 2012). The
tively involved in the CMI, while the B-lymphocyte plays a vital role in anti-inflammatory properties of corticosteroids results in a decrease in
HI. Both the CMI and the HI maintain the balance to ensure that im- phagocytic cell activity and alter lymphocyte function (Caroprese et al.,
mune function remains effective, which can be inhibited during ex- 2012). Heat stress influences the immune system by altering the
posure to stressors (Smith and Vale, 2006). Th1:Th2 ratio as the immune system attempts to maintain homeostasis,
With increasing prevelence and intensity of adverse weather events, however shifts from homeostasis may result in animals becoming im-
dairy cattle may become increasingly susceptible to heat stress. In re- munocompromised and subsequently become more susceptible to dis-
sponse to future climate change projections, suitable amelioration eases (Elenkov et al., 2000). Therefore, maintaining the Th1:Th2 bal-
strategies need to be developed to maintain the health, productivity and ance could be a critical factor in minimising the impact of
well-being of dairy cattle during periods of heat stress. Therefore, the immunological challenges during the summer season.
purpose of this review is to describe the influence of heat stress on the
immune system of dairy cattle. This may provide valuable information 4. Impact of heat stress on immune responses of dairy cattle to
towards understanding and identifying appropriate amelioration stra- vaccination
tegies to maintain the integrity of the immune system of dairy cattle
during periods of extreme climate. Heat stress is associated with numerous health concerns in livestock
and is also associated with limiting an animal's ability to build an im-
2. Heat stress and dairy cattle production mune response. Administering vaccines in cattle during periods of heat
stress may not allow for the development of an optimum immune re-
Dairy cattle experience heat stress when they are exposed to en- sponse, therefore potentially rendering the vaccine ineffective (Hu
vironmental conditions above their thermo-neutral zone. As heat stress et al., 2007). Furthermore, heat stress reduces the natural barriers of an
increases there is a reduction in DMI, growth, feed conversion effi- animal to bacteria and also potentially increases the level of endotoxin,
ciency (Brown-Brand et al., 2005), reproductive performance (Jordan, which may have further undesirable effects on vaccines containing
2003), milk production, and milk quality (Wheelock et al., 2010; whole cells of target bacteria (Lambert, 2009). Glucocorticoids released
Rhoads et al., 2009). Heat stress is also associated with hypofunction of during heat stress activate latent viruses, via i) directly acting on the
the thyroid gland which subsequently results in reduced metabolic heat viral genome, and by ii) decreasing the immunological memory re-
production (Omidi et al., 2015). Therefore, reduction in thyroid hor- sponses. Chronic heat stress negatively impacts the immune system in
mone concentration can be considered as an adaptive mechanism to mice and increases their susceptibility to infections by increasing the
reduce metabolic heat production during periods of hot climatic con- number of CD4+, CD25+, Foxp3+, IL-10 and TGF-β which is asso-
ditions (Lacetera et al., 1996). ciated with a suppression of the adaptive immune response (Meng et al.,
2013). Hu et al. (2007) reported that chronic heat stress negatively
3. Interaction between heat stress and the immune system of influenced the immune responses of DNA vaccination by impairing the
dairy cattle CMI. Overall these studies suggest that heat stress negatively influences
the responsiveness of the ruminant immune system.
The SAM and HPA axis play an integral role in regulating responses
to stressors. Stimulation of the HPA axis results in the production of 5. Molecular mechanisms governing immune responses during
cortisol, which is associated with a suppression of the immune system heat stress in dairy cattle
in cattle (Grandin, 1997). Fig. 1 highlights the various impacts of heat
stress on the immune response of dairy cattle. The effect that heat stress Heat stress elicits numerous physiological and cellular adaptation in
has on inducing glucocorticoids is varied due to the different cytokines an attempt to counteract the impact of stress and to protect the body
produced (Elenkov, 2004). However, the inhibition of cytokine pro- from its harmful effects (Sonna et al., 2002). These mechanisms help in
duction by glucocorticoids may be a protective mechanism in an at- the elimination of pathogens, both specifically and non-specifically.
tempt to prevent excessive immune suppression. Glucocorticoids in- Cortisol efficiently negates the heat stress response and has an anti-
fluence the balance of T-helper 1 (Th1) and T-helper 2 (Th2) through inflammatory influence on the immune response, whilst catecholamines
the inhibition of IL-12, whereas catecholamines inhibit IL-12 and en- are considered to have an inflammatory effect (Kovács et al., 2000).
hanced IL-10 production (Sophia et al., 2016). Therefore, glucocorti- Therefore, heat stress negatively influences the immune response by
coids and catecholamines may suppress cellular immunity and result in stimulating HPA and SAM axis, followed by the stimulation of the
a preferential shift towards Th2-mediated HI (Elenkov et al., 2000). primary and the secondary lymphoid organs resulting in the production
The response of the immune system is one of the mechanisms de- of antibodies, cytotoxic cells, cytokines, chemokines and heat shock
veloped to defend against environmental challenges (Stephanou et al., proteins (HSPs) (Collier et al., 2008; Evans et al., 2015). The genes
2011). One common theory is that stressors suppress components of the regulating stressor proteins such as HSPs, NOD-like receptors (NLRs),
immune system, thus enhancing the susceptibility of an animal to dis- Toll-like receptors (TLRs), RIG-I like receptors (RLRs), C-type lectin
ease. Heat stress stimulates the signal transduction pathways, altering receptors (CLRs), the AIM2-like receptors (ALRs), cytokines and che-
gene expression of the immune cell mediators resulting in the activation mokines also play a vital role in the regulation of the immune system
of the heat shock response promoting cytokine activity. Distinct cyto- (Vidya et al., 2018).
kine patterns are responsible for the effector functions and development Cortisol regulates the immune system by targeting the genes related
of Th1 and Th2 cell responses. T-helper 1 cells activate cellular im- to cytokines, chemokines, inflammatory proteins and their receptors as
munity and inflammatory responses, whereas Th2 cells regulate HI and well as cell adhesion (Löwenberg et al., 2008; Cruz-Topete and
promote anti-inflammatory responses (Hendrix and Nitsch, 2007). The Cidlowski, 2015a, 2015b). At the transcription level cortisol binds to
ability of animals to selectively produce Th1 cytokines (IFN-γ and IL- the glucocorticoid receptor to repress the transcriptional activity of the
12) and Th2 cytokines (IL-10, IL-4, IL-13) is an important component in activator protein-1 (AP-1) and NF-κB, thus regulating the expression of
regulating the Th1:Th2 cytokine balance (Park et al., 2005). Hy- various cytokines (Liberman et al., 2007; Busillo and Cidlowski, 2013).
perthermia is associated with a down regulation of Th1 cytokines and Cortisol inhibits MAPK signalling pathways, through MAPK phospha-
an upregulation of Th2 cytokines, thus suppressing the CMI (Webster, tase-1 which causes inhibition of p38 MAPK repressing multiple
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M. Bagath, et al. Research in Veterinary Science 126 (2019) 94–102
Fig. 1. Description of various impacts of heat stress on the immune system in dairy cattle.
inflammatory genes (Wu et al., 2005). As cortisol concentrations in- 7. Heat stress and innate immunity and leukocyte population in
crease and bind with its receptors, there is an inhibitory effect on the dairy cattle
immune system which is associated with a repression on the anti-in-
flammatory action of immune cells. Depending on the stimuli, various components of the immune
Under in vitro conditions the polymorphonuclear cells exposed at system may be activated. The innate immune response is the first line of
39 °C and 41 °C did not show any change in the caspase-3 and caspase-7 defense that acts immediately when the body is exposed to an infection
activity respectively, however there were changes in the phagocytosis or immune challenge (Medzhitov, 2007). It includes physical barriers
and ROS production when exposed to 41 °C (Lecchi et al., 2016). Min such as the skin and mucosal membranes, mucosal secretions, tears,
et al. (2016) showed that during heat stress condition in dairy cows 85 saliva, urine, digestive and vaginal acids. If these physical barriers fail
proteins were differentially abundant, while the complement compo- to eliminate the pathogen, then the innate immune system responds by
nents C1, C3, C5, C6, C7, C8, and C9, complement factor B, and factor H facilitating the migration of neutrophils, monocytes (in the blood), and
were down-regulated. These results imply that the immune system of macrophages (in the tissue) to the site of infection and use invariant
these dairy cows exposed to heat stress was compromised. The immune receptors to detect a wide array of pathogens (Sophia et al., 2016).
system within the udder is also compromised via the suppression of Upon detecting a pathogen, these cells phagocytize the pathogen by
CMI, thus facilitating the risk of infection, apoptosis of mammary cells engulfing and kill the pathogenic organism by endolysosomal path-
and reduced milk production (Thompson-Crispi et al., 2014). ways. Innate immunity provides priming opportunity and allows for the
development of the adaptive immune system to produce antibodies
against target pathogens (Janeway, 1999).
6. Role of heat stress and HSPs in immunity Leukocytes form the principal components of the immune system,
their primary function is to protect and defend the body against the
Intracellular HSPs, particularly HSP70 and HSP90, are involved in invading infectious agents such as bacteria, viruses, fungi, and parasites
antigen processing and presentation, in addition to their functions as (Chandra et al., 2012). Leukocyte population is affected under heat
molecular chaperones (Archana et al., 2017). Heat shock proteins are stress condition in dairy cattle (Lacetera et al., 2005). Salem (1980)
associated with the cytoplasmic antigenic peptide and aid in the peptide reported that leukocyte concentration decreased during summer in both
translocation and processing (Ishii et al., 1999). The HSP70 family are cows and buffaloes. Gwazdauskas et al. (1980) indicated that total
associated with the transporters affiliated with antigen processing leucocyte counts and differential leucocyte counts were altered in re-
(TAP) and require ATP-for transportation of antigenic peptides from the sponse to chronic stress in cattle. The increase in leukocytes is sug-
cytosol to the endoplasmic reticulum (Kamiguchi et al., 2008). Heat gestive of an altered immunological activity in buffalo calves exposed
shock proteins are also associated with the TLR pathways, where HSP70 to acute thermal shock (Omran et al., 2013). Chandra et al. (2012)
and HSP60 play a role in the stimulation of TLR4 for the proliferation of reported that the mean values of leukocytes varied from 12.37 ± 0.74
dendritic cells (DC) (Fang et al., 2011). Damaged cells in an affected to 14.34 ± 0.55 (×103cells/μl) and from 9.53 ± 0.67 to
area release HSPs that activate DC, thus inducing inflammatory reac- 13.57 ± 0.23 (× 103cells/μl) in growing and adult Sahiwal cows,
tions by secreting inflammatory cytokines. Increase in the duration of respectively during summer seasons under in vivo conditions. The mean
stress leads to more damaged cells, which are positively correlated with concentrations of total leukocytes in Tharparkar and Karan Fries cattle
an increasing amount of extracellular HSPs and innate immune re- varied from 13.72 ± 0.52 to 13.88 ± 0.73 and 12.76 ± 0.58 to
sponse (Calderwood et al., 2016). This suggests that HSPs have a role in 13.20 ± 0.40 (× 103cells/μl), respectively, when exposed to different
boosting the innate immunity.
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M. Bagath, et al. Research in Veterinary Science 126 (2019) 94–102
temperature conditions and it was concluded that there were no sig- cows to heat stress under in vitro conditions resulted in the decline of
nificant difference in the total leukocyte count in both breeds (Pandey lymphocyte proliferation in culture incubated for 60 h at 42 °C after
et al., 2017). Abdel-Samee (1987) reported that leukocytes increase by stimulation with mitogens. Similarly, Kamwanja et al. (1994) reported
21–26% in Friesian cattle under heat stress conditions due to thyr- that the exposure of bovine lymphocytes to a heat shock of 45 °C for 3 h
omolymphatic involution. Nouty et al. (1986) observed higher total under in vitro conditions decreased the number of viable cells and re-
leukocytes count during summer months as compared to other seasons duced the PBMC response to mitogens. The impaired function of bovine
in Holstein breed of cattle and they attributed this to the heat stress lymphocytes during periods of heat stress may be associated with re-
experienced by these animals during summer season. The mean total duced cellular immunity, which influences the Th1 and Th2 balance in
leukocytes were higher in summer than in monsoon or winter (Naik favor of the secretion of Th2 cytokines ultimately affecting lymphocyte
et al., 2013). This could be due to release of corticosteroids or epi- proliferation (Lacetera et al., 2005; Lacetera et al., 2006). Exposure of
nephrine hormones due to summer stress which in turn increased leu- bovine lymphocytes under in vitro heat shock reduced the lymphocyte
kocyte count (Jain, 1993). proliferation response to mitogen and reduction in the number of viable
A study conducted on young calves under different housing condi- cells in Angus cattle (Elvinger et al., 1991). In cows, heat stress had an
tions it was established that neutrophil levels increased and the number immunosuppressive effect on lymphocyte proliferation in response to
of lymphocytes were lower in animals that were stalled compared to the T cell mitogen Con An under in vitro conditions (Lacetera et al.,
housed animals in loose house system (Friend et al., 1987). Stull and 2006). The proportion of lymphocyte and neutrophil has been reported
McMartin (1992) reported that the neutrophils to lymphocytes (N:L) to increase during summer months compared with monsoon and winter
ratio were higher during heat stress exposure. The mean neutrophil seasons in Punganur cattle under in vivo conditions (Naik et al., 2013).
count was significantly higher in summer than in winter and monsoon Similarly, Narayan et al. (2007) reported that in Holstein Friesian ×
seasons because of high heat stress incidence during the summer Sahiwal cross breeds lymphocyte count increased during in vivo heat
months in Punganur bred of cattle under in vivo studies (Naik et al., stress studies. Numerous studies have evaluated the relationships be-
2013). This increase might be due to an accelerated mobilization of tween heat stress and cellular immune function in bovines (Elvinger
mature neutrophils from marrow, due to the release of glucocorticoids et al., 1991; Soper et al., 1978; Kamwanja et al., 1994; Kelley et al.,
during heat stress (Jain, 1993). This finding was in contrary to the re- 1982a; Lacetera et al., 2002). However, there is some conjecture re-
sults reported by Narayan et al. (2007) who observed a decrease in garding the impact of heat stress on lymphocyte function, where some
neutrophil count during summer in Holstein-Friesian crossbred cows authors have reported an improvement (Soper et al., 1978), an im-
under in vivo conditions. pairment (Elvinger et al., 1991; Kamwanja et al., 1994) and no influ-
Lymphocytes are involved in a variety of immunological functions ence of heat exposure (Lacetera et al., 2002; Kelley et al., 1982b).
such as immunoglobulin production and modulation of immune de-
fense (Campbell, 1996). Heat stress was established to negatively in- 9. Heat stress impact on humoral immune response in dairy cattle
fluence the lymphocyte proliferation under in vitro conditions (Lacetera
et al., 2005; Kamanga-Sollo et al., 2011). Elvinger et al. (1991) reported Heat stress is associated with decreased milk production, impaired
that lymphocyte from Holstein cows at high temperature (42 °C) for reproduction and increased disease incidence in lactating dairy cows. In
60 h showed a reduction in proliferation compared with incubation at dry cows, heat stress has been reported to affected milk yield in the
38.5 °C during in vitro studies. However, there were no effects in Hol- subsequent lactation and compromised the immune function during the
stein cows during in vivo conditions. Further, Lacetera et al. (2006) transition period (Collier et al., 2006a, 2006b; Do-Amaral et al., 2010;
showed that at 41 °C and 42 °C lymphocyte proliferation under in vitro Do-Amaral et al., 2011; Tao et al., 2012). High ambient temperature
conditions declined in both Brown Swiss and Holstein cows. There was during late gestation also influences the transfer of passive immunity to
also a significant decrease in the lymphocyte counts and an increase in the calf. Calves exposed to heat stress had lower serum IgG levels than
neutrophil counts in Sahiwal and Karan Fries heifers when exposed to the calves in a cool environment (Tao et al., 2012). This may indicate
40 °C (Mayengbam, 2008). Furthermore, it was established that the that passive immune transfer in calves exposed to heat stress in-utero is
monocytes count increased during summer and this was attributed to compromised, which may be associated with impaired IgG absorption
the increased cortisol secretion (Jain, 1993). However, under in vivo in the intestine in post-natal life (Tao et al., 2012). Increased plasma
conditions the mean eosinophil count was established to be lower concentrations of IgG has been reported during late gestation in heifers
during summer and higher during monsoon in Punganur cattle (Naik in the heat stressed groups, whereas non-heat stressed heifers showed
et al., 2013). Similarly, the mean basophil count was statistically lower lower plasma concentrations of IgG due to the diversion of antibodies
under in vivo conditions in summer as compared to either monsoon or from the bloodstream to colostrums (Nardone et al., 1997). These au-
winter in Holstein-Friesian crossbred cows (Narayan et al., 2007). thors suggested that heat stress has a negative effect on the transfer of
maternal immunoglobulin to colostrum in dairy cows exposed to the
8. Heat stress impact on cell-mediated immune response in dairy hot environment. In addition, Nardone et al. (1997) also reported that
cattle colostrum from heat stressed dairy cow contained lower IgGs (22.3%
less) than the cows kept in the cooler environments. However Shearer
The adaptive immune system is composed of both cellular and hu- et al. (1992) observed higher concentrations of IgG in colostrum of
moral responses (Elenkov, 2008). However, studies on the impact of cows exposed to natural summer heat than cows exposed to other
heat stress on CMI of cattle are inconclusive (Lacetera et al., 2006). season of the year. Table1 describes the impact of heat stress on the
Under in vitro condition, peripheral blood mononuclear cells (PBMC) humoral immune system in dairy cattle.
are affected under heat stress conditions in cattle and buffaloes and the There are diverse reports on the impact of heat stress on the hu-
responses are variable depending on the physiological state of the an- moral immune response in livestock (Lacetera et al., 2006; Bhan et al.,
imals (Lacetera et al., 2006). Hot weather increased the proliferation of 2012; Pandey et al., 2017). As described in Table 1 the impact of heat
PBMC in cows in a temperate climate under in vitro conditions (Soper stress on the leukocyte population varied among the studies in dairy
et al., 1978). Lacetera et al. (2006) observed that the PBMC isolated and cattle. In most of the studies the leukocyte population decreased
stimulated with concanavalin A from both Brown Swiss and Holstein (Gwazdauskas et al., 1980; Elvinger et al., 1991; Lacetera et al., 2006)
cows showed that the Holstein PBMC were more tolerant to heat stress while in few studies it increased (Nouty et al., 1986; Omran et al., 2013;
than the Brown Swiss during chronic heat stress exposure under in vitro Naik et al., 2013). However, there are also reports describing no effect
conditions. of heat stress on leukocyte population in dairy cattle (Pandey et al.,
Elvinger et al. (1991) reported that exposure of lactating Holstein 2017; Pandey et al., 2017). These differences of heat stress on the
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M. Bagath, et al. Research in Veterinary Science 126 (2019) 94–102
Table 1
Description of heat stress impact on humoral immune response in dairy cattle.
Stress Animal Effect on leukocytes References
Summer stress Holstein-Friesian cows and buffaloes Leukocytes decreases Salem (1980)
Chronic stress Holstein-Friesian cows Leukocytes decreases Gwazdauskas et al. (1980)
Summer Holstein cows Leukocytes Increases Nouty et al. (1986)
Heat stress Friesian cows Leukocytes Increases Abdel-Samee (1987)
Summer stress Sahiwal cow Leukocytes decreases Bhan et al. (2012)
Heat stress Buffalo Leukocytes Increases Omran et al. (2013)
Summer Punganur cattle Leukocytes Increases Naik et al. (2013)
Heat stress Tharparkar and Karan Fries heifers No changes Pandey et al. (2017)
Heat stress Angus cattle Lymphocytes decreases Elvinger et al. (1991)
Heat stress Holstein cows Lymphocytes decreases Kamwanja et al. (1994)
Heat stress Brown Swiss and Holstein cows Lymphocytes decreases Lacetera et al. (2006)
Heat stress Buffalo Lymphocytes decreases Devaraj and Upadhyay (2007)
Heat stress Holstein-Friesian cow Neutrophils decreases Narayan et al. (2007)
Lymphocyte increases
No changes in Eosinophils
Heat stress Sahiwal and Karan Fries heifers Neutrophils increases Mayengbam (2008)
Summer stress Punganur cattle Neutrophils and lymphocytes increases Naik et al. (2013)
Summer stress Tharparkar and Karan Fries No changes Pandey et al. (2017)
Heat stress Tharparkar and Karan Fries heifers No changes in Neutrophil, lymphocytes and monocytes Pandey et al. (2017)
leukocyte population across the studies could be attributed to the breed expression in bovine mammary tissues subjected to heat stress. Hall
difference. Generally it was observed that in indigenous breeds the level et al. (2014) reported higher expressions of IL-18 receptor and RANTES
of leukocytes increased after exposure to heat stress in dairy cattle cytokine in Holstein cows supplemented with OmniGen-AF (Anti-
(Mayengbam, 2008; Naik et al., 2013; Pandey et al., 2017) while in caking agent with B-complex vitamins) during heat stress exposure.
majority of the studies its level increased in exotic breeds (Nouty et al., These results suggest that OmniGen-AF may improve immune function
1986; Abdel-Samee, 1987). in cows exposed to heat stress, thus providing an opportunity negate the
Godden (2008) reported that exposure of cows to heat stress during impact of heat stress on the immune system.
late pregnancy reduced colostrum quality, with lower concentrations of
IgG, IgA along with a reduced total protein, casein, lactalbumin, fat,
and lactose. Similarly, Adin et al. (2009) reported that multiparous 11. Proposed strategies to improve immune competency of dairy
Holstein dry cows exposed to heat stress showed a reduction in milk cattle during heat stress
yield and its IgG contents in subsequent lactation. Bernabucci et al.
(2013) reported that colostrum of heat-stressed cows contained lower Ameliorative strategies to support immune system during periods of
levels of casein, lactalbumin, and reduced concentrations of IgG and heat stress could be achieved by adopting suitable management stra-
IgA, but did not affect the percentage of lactoglobulin or the con- tegies. Mitigation management in production species can be achieved
centration of IgM. These changes in colostrum may be attributed to the by three major pathways i) physical modification of the environment;
negative impact of heat stress on DMI resulting in nutritional restric- ii) improved nutritional management; and iii) genetic and phenotypic
tion, reduced mammary blood flow resulting in impaired transfer of IgG selection for thermo-tolerance. The animals must be maintained on
and nutrients from the blood circulation to the mammary gland, and/or quality feed with low fibre and optimum protein and energy (Sejian
impaired immune response of mammary gland plasma cells that pro- et al., 2015). The incorporation of appropriate energy, minerals, vita-
duce IgA (Godden, 2008). mins, antioxidants, prebiotics and probiotics with balanced nutrition
are highly essential to ameliorate heat stress in dairy cows (Smith et al.,
1997; Popovic, 2004; Paulrud, 2005). Amino acids play a vital role in
10. Heat stress impact on immune system-related gene expression the immune response during heat stress in dairy cows, as the utilisation
patterns in dairy cattle of amino acids for milk production is decreased and more emphasis is
given to immune response and gluconeogenesis (Guo et al., 2018). The
When exposed to increasing THI, lactating cows showed a decrease supplementation of selenium reduced the frequencies of clinical mas-
in leukocyte number along with the decreasing TNF-alpha and IL-10 titis and somatic cell count in heat stressed dairy cows (Smith et al.,
cytokines (Zhang et al., 2014). Similarly, the TNFα production was 1997). The incorporation of zinc in the diets of dairy cattle during
decreased and cows had an increase in SOCS-1 and SOCS-3 lymphocyte summer, facilitated in keratinization of keratin layer of udder and may
mRNA differential expression in multiparous Holstein cows (Do-Amaral be associated with a reduction in the incidence of mastitis (Popovic,
et al., 2010). Additionally, multiparous Holstein cows subjected to heat 2004. Paulrud, 2005). Similarly, supplementation of zinc to heat
stress for a period of 46 days before calving showed lesser hepatic PRL- stressed PBMC subjected at 42 °C collected from periparturient Sahiwal
R, SOCS-3, and CAV-1 level compared to control animals in the hepatic and Karan Fries dairy cows, showed attenuation of HSPs response and
mRNA expression (Do-Amaral et al., 2011). Further, the hormones augments the immunity in the PBMC by decreasing the IL-6 level in the
prolactin and cortisol has been shown to exert influences over the HSPs serum (Sheikh et al., 2017). Furthermore, the supplementation of
expression associated with immune responses in cows subjected to heat gamma-aminobutyric acid also decreased IL-4, IL-6, IL-2, and TNF-a in
stress (Collier et al., 2008). Table 2 describes the impact of heat stress a dose dependent manner in the heat stressed dairy cows (Cheng et al.,
on the immune system related gene expression in dairy cattle. 2016). Copper and iron supplementation augmented the development
Thompson et al. (2014) reported higher IL-10 expression in heat of immune organs such as thymus, spleen, lymph node and enhances
stressed cows compared with cows housed under thermoneutral con- the phagocytic activity of neutrophils and macrophages which are es-
ditions. Similarly, Italian Friesian cows subjected to heat stress, with sential for the proliferation of immune cells and antibody production
average THI of 72, showed an increase in serum IL-10 secretion in heat (Lukasewycz and Prohaska, 1990). Further, Vivier et al. (2008) also
stressed animals (Caroprese et al., 2009). Furthermore, Dado-Senn et al. reported that supplementation of chromium helped in the development
(2018) reported increased IL34, IL27RA, IL6R, IL10RB and IL1R1 of primary immune responses with increased IgM and IgG.
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M. Bagath, et al. Research in Veterinary Science 126 (2019) 94–102
on the decrease in the IL-1 in serum and also with IL-1 downregulation
Cells or tissue
ment in the immune function of the dairy cows (Shan et al., 2018).
Feeding of heat stressed animals with yeasts and plant extracts may
exert a positive effect in rumen metabolism and regulates the body
temperature (Conte et al., 2018). The addition of probiotics in the feed
improved the animal's health by inhabitating the whole digestive tract
and fortified the intestinal mechanical barriers to prevent the entry of
microbial pathogens (Popovic, 2004). Further, the combination of
prebiotics and probiotics activated phagocytosis and enhanced cytokine
the cytokine expression of IL34, IL27RA, IL6R, IL10RB, IL1R1 were up-regulated
HSP70 mRNA and protein expression. Under the heat stressed in vivo
conditions, Holstein cows supplemented with Zymosan had enhanced
DMI, milk yield, increased IgA, IL-2, TNF-α in serum, however hepatic
Increased IL10
Impact of HS on immune system related gene expression in dairy cattle.
THI – 72
12. Conclusion
THI
Heat stress acts as the major challenge for maintaining the immune
–
–
–
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ameliorate heat stress induced damage to immune functions in dairy Collier, R.J., Dahl, G.E., VanBaale, M.J., 2006b. Major advances associated with en-
cows. vironmental effects on dairy cattle. J. Dairy Sci. 89, 1244–1253.
Collier, R.J., Collier, J.L., Rhoads, R.P., Baumgard, L.H., 2008. Invited review: genes in-
volved in the bovine heat stress Response1. J. Dairy Sci. 91, 445–454.
13. Future perspectives Conte, G., Ciampolini, R., Cassandro, M., Lasagna, E., Calamari, L., Bernabucci, U., Abeni,
F., 2018. Feeding and nutrition management of heat-stressed dairy ruminants. Ital. J.
Anim. Sci. 17, 604–620.
Future research needs to evaluate broader aspects of the impact of Cruz-Topete, D., Cidlowski, J.A., 2015a. One hormone, two actions: anti- and pro-in-
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