LeakyCow – Heat stress-induced local and systemic immune responses in dairy cows with `leaky gut syndrome`
Final Report Abstract
Climate change is expected to increase the frequency of extreme weather events, such as heat waves, in the coming years. Heat-stressed dairy cows reduce feed intake, milk yield, reproductive performance and are at increased risk of diseases. In order to increase heat loss, the blood circulation is directed away from the visceral area towards the skin. The local blood flow in the splanchnic area is reduced, leading to local hypoxia episodes in the gastrointestinal tract, increasing gut permeability. However, little is known about the onset of a local and/or systemic immune response activated by penetrated pathogens and bacteria from the gastrointestinal tract, and whether the increase in ambient temperature might also lead to microbial dysbiosis linking endotoxemia, `leaky gut` and immune response. The aim of this study was to elucidate the negative effects of high ambient temperatures on the humoral immune response in mesenteric lymph nodes and peripheral blood mononuclear cells (PBMCs) and its interaction with the intestinal gut microbiota in lactating Holstein cows. Thirty dairy cows were assigned to either a control (CON; 16°C, temperaturehumidity-index (THI) 60, ad libitum), heat-stressed (HS; 28°C, THI 76, ad libitum) or pair-feeding (PF; 16°C, THI 60, restricted feeding to HS cows) group for seven days of treatment. The PF group mirrored the reduced feed intake behaviour of the HS group. The local immune response in the mesenteric lymph nodes (MLN) were characterized by the activation of the Toll-like receptor 2 signaling pathway, which induce proinflammatory cytokine production, e.g. tumor necrosis factor α (TNFα) and interferon γ (IFNγ). However, chemokines regulating the leucocyte trafficking between the MLN and the gut seem not to be involved in the adaptive immune response to heat stress. In the systemic blood circulation, proinflammatory cytokines and the acute phase protein haptoglobin were induced by circulating endotoxin. Furthermore, RNA sequencing of PBMCs revealed that heat stress activates vasoconstriction, platelet activation and the coagulation cascade with concomitant leucocyte trafficking during heat stress, potentially caused by microvascular injuries and fluid shear stress due to altered blood flow. Moreover, specific immune pathways related to the T cell receptor signaling pathway, antigen processing and presentation, and intestinal immune network for IgA production, as well as metabolic pathways related to lysine degradation and lipid metabolism, were down-regulated, implying immunosuppression of lymphocytes and metabolic adaptation to lower nutrient availability during HS. Moreover, the reduction in feed intake during HS had significant effects on microbial diversity and the abundance of certain taxa, e.g. unclassified Clostridia, Succinivibrionaceae UCG-001, Colidextribacter, Lachnospiraceae UCG-008, which could provide a potential source of pathogens and messenger molecules facilitating the activation of the immune response in the gastrointestinal tract, underpinning the importance of maintaining intestinal homeostasis.
Publications
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GfE 2022 – Gesellschaft für Ernährungsphysiologie (virtual) Impact of ambient heat on leucocytic HSP70 expression, NF-κB p65 translocation, and hematology in primiparous Holstein dairy cows
Koch F., Hansen C., Viergutz T. & Kuhla B.
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ICPD 2022 – International Conference on Production Diseases in Farm Animals (Madison, WI, USA) Heat stress effects on the mucosa-associated and digesta microbiome in the jejunum of primiparous dairy cows
Koch F., Reyer H., Wimmers W. & Kuhla B.
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ISEP 2022 – International Symposium on Energy and Protein Metabolism and Nutrition (Granada, Spain) Heat stress affects metabolic profile and immune response in mesenteric lymph nodes of dairy cows
Koch F. & Kuhla B.
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ADSA 2023 – American Dairy Science Association (Ottawa, Canada) Proteomic analysis expose new insights into adaptation mechanisms of the mammary gland to heat stress in dairy cows
Koch F., Albrecht D. & Kuhla B.
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GfE 2023 – Gesellschaft für Ernährungsphysiologie (Göttingen, Germany) Mild heat stress increases ruminal acetate synthesis and alters milk composition of primiparous Holstein dairy cows
Koch F., Hansen C. & Kuhla B.
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GfE 2023 – Gesellschaft für Ernährungsphysiologie (Göttingen, Germany) Mild heat stress is associated with immunological and metabolic changes in peripheral blood mononuclear cells of primiparous Holstein dairy cows
Koch F., Kuhla B. & Kühn C.
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Mild heat stress–induced adaptive immune response in blood mononuclear cells and leukocytes from mesenteric lymph nodes of primiparous lactating Holstein cows. Journal of Dairy Science, 106(4), 3008-3022.
Koch, Franziska; Otten, Winfried; Sauerwein, Helga; Reyer, Henry & Kuhla, Björn
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Cellular and mitochondrial adaptation mechanisms in the colon of lactating dairy cows during hyperthermia. Journal of Dairy Science, 107(5), 3292-3305.
Eslamizad, Mehdi; Albrecht, Dirk; Kuhla, Björn & Koch, Franziska
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DAFA 2024 – Deutsche Agrarforschungsallianz (Potsdam, Germany) Heat stress-induced inflammatory processes in dairy cows and mitigation strategies
Koch F. & Kuhla B.
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EAAP 2024 - Annual Meeting of the European Federation of Animal Science (Florence, Italy) Time-dependent molecular adaptation of immune and platelet function to heat stress in PBMC of Holstein dairy cows
Koch F., Kuhla B. & Kühn C.
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GfE 2024 – Gesellschaft für Ernährungsphysiologie (Göttingen, Germany) Short-term effects of thermal heat and LPS-challenge on inflammatory cytokines and Toll-like receptor 4 signaling in bovine leukocytes of mesenteric lymph nodes – an in vitro study
Koch F. & Kuhla B.
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Heat stress and feeding effects on the mucosa-associated and digesta microbiome and their relationship to plasma and digesta fluid metabolites in the jejunum of dairy cows. Journal of Dairy Science, 107(7), 5162-5177.
Koch, Franziska; Reyer, Henry; Görs, Solvig; Hansen, Christiane; Wimmers, Klaus & Kuhla, Björn
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Novel Perspective on Molecular and Cellular Adaptations of the Mammary Gland-Regulating Milk Constituents and Immunity of Heat-Stressed Dairy Cows. Journal of Agricultural and Food Chemistry, 72(37), 20286–20298.
Koch, Franziska; Albrecht, Dirk; Albrecht, Elke; Hansen, Christiane & Kuhla, Björn
