# A new type of biomarker for heat stress: insights from immunology

**Authors:** Chunmei Ye, Zhipeng Zhang, Zhangping Yang

PMC · DOI: 10.3389/fimmu.2026.1742202 · Frontiers in Immunology · 2026-02-12

## TL;DR

This paper explores how heat stress affects dairy cows' immune systems and proposes new immune-related biomarkers to better predict and manage heat stress impacts.

## Contribution

The paper introduces immune-related biomarkers as a novel strategy for early warning and individualized assessment of heat stress in dairy cows.

## Key findings

- Heat stress reduces intestinal tight junction proteins by ~40%, increasing endotoxin translocation and mastitis risk.
- Heat stress impairs T/B cell function, lowers CD4+/CD8+ T cell ratio, and reduces immune memory formation.
- Biomarkers like HSPs, NLR, cytokine profiles, and epigenetic markers offer targets for heat-tolerant breeding and early intervention.

## Abstract

Global warming exacerbates heat stress in dairy cows, while traditional indicators like the Temperature-Humidity Index (THI) struggle to accurately reflect individual physiological response variations. This review systematically analyzes the dynamic changes in the bovine immune system under heat stress and proposes immune-related biomarkers as a novel strategy for early warning and individualized assessment. Research reveals that heat stress compromises the innate immune barrier function of cows, suppressing neutrophil chemotaxis and antimicrobial peptide synthesis, leading to a decline in the opsonophagocytic index and endotoxin translocation. Expression of intestinal tight junction proteins (e.g., Claudin-1, Occludin) is significantly downregulated (by ~40%), causing endotoxin translocation (serum LPS increases ~3-fold) and disruption of the blood-milk barrier, increasing mastitis risk by 2–3 times. Regarding adaptive immunity, the proliferation and differentiation of T/B cells are impaired, the CD4+/CD8+ T cell ratio decreases, antibody affinity maturation is suppressed, and the efficiency of immune memory formation post-vaccination is reduced. Concerning mammary immunity, the number of viable granulocytes in milk decreases, mammary epithelial cells increase, pro-inflammatory cytokine levels rise, and the risk of clinical mastitis increases 2–3 fold. Furthermore, heat stress induces metabolic reprogramming, gut microbiota dysbiosis, oxidative stress, and activation of the hypothalamic-pituitary-adrenal (HPA) axis. Novel biomarkers, such as Heat Shock Proteins (HSPs), Neutrophil-to-Lymphocyte Ratio (NLR), cytokine profiles (e.g., IL-6/TNF-α), acute-phase proteins (e.g., Haptoglobin, Hp), and epigenetic markers, provide crucial targets for heat-tolerant breeding and early intervention, promising to enhance the climate resilience of the dairy industry.

## Linked entities

- **Proteins:** CLDN7 (claudin 7), si:ch73-61d6.3 (uncharacterized si:ch73-61d6.3), HP (haptoglobin), IL6 (interleukin 6), TNF (tumor necrosis factor)
- **Diseases:** mastitis (MONDO:0006849)

## Full-text entities

- **Genes:** CLDN1 (claudin 1) [NCBI Gene 414922], AICDA (activation induced cytidine deaminase) [NCBI Gene 539888] {aka AID}, IFNG (interferon gamma) [NCBI Gene 281237], HP (haptoglobin) [NCBI Gene 280692], ARG1 (arginase 1) [NCBI Gene 513608], OCLN (occludin) [NCBI Gene 512405], PRL (prolactin) [NCBI Gene 280901] {aka GHA1, Prol}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 280828] {aka IL-8, IL8}, IL10 (interleukin 10) [NCBI Gene 281246] {aka IF2A}, CD4 (CD4 molecule) [NCBI Gene 407098], LOC517016 (interleukin 6 (interferon, beta 2)) [NCBI Gene 517016] {aka IF1DA6}, HSP90AB1 (heat shock protein 90 alpha family class B member 1) [NCBI Gene 767874] {aka HSPCB}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 407152] {aka cd45}, LOC781146 (lysozyme) [NCBI Gene 781146], IL2 (interleukin 2) [NCBI Gene 280822] {aka IL-2, TCGF}, CLDN3 (claudin 3) [NCBI Gene 404153], TNF (tumor necrosis factor) [NCBI Gene 280943] {aka TNF-a, TNF-alpha, TNFa}, TLR4 (toll like receptor 4) [NCBI Gene 281536], HSPA1A (heat shock protein family A (Hsp70) member 1A) [NCBI Gene 282254] {aka HSP70, HSP70-1, HSP70-2, HSPA1, HSPA1B, HSPA2}, IL1B (interleukin 1 beta) [NCBI Gene 281251], SAA2 (serum amyloid A2) [NCBI Gene 506412] {aka SAA, SAA1}, LOC524810 (IgM) [NCBI Gene 524810] {aka IGHV, IGHV1S15, IGHV1S16, IGHV1S17}, LTF (lactotransferrin) [NCBI Gene 280846] {aka Lf}
- **Diseases:** Immune system (MESH:D007154), endocrine dysregulation (MESH:D004700), hypoglycemia (MESH:D007003), infection (MESH:D007239), cytotoxic (MESH:D064420), endotoxemia (MESH:D019446), inflammatory storm (MESH:C566109), bacterial or fungal infections (MESH:D009181), mammary infectious disease (MESH:D003141), memory impairment (MESH:D008569), tissue damage (MESH:D017695), bacterial infections (MESH:D001424), Dysbiosis (MESH:D064806), water (MESH:D000069578), anorexia (MESH:D000855), Metabolic disturbances (MESH:D024821), respiratory infection (MESH:D012141), chronic inflammation (MESH:D007249), mitochondrial dysfunction (MESH:D028361), respiratory diseases (MESH:D012140), fever (MESH:D005334), Mastitis (MESH:D008413)
- **Chemicals:** RNS (MESH:D026361), Butyrate (MESH:D002087), Niacin (MESH:D009525), selenium (MESH:D012643), MDA (MESH:D008315), free (-), T4 (MESH:D013974), polyunsaturated fatty acid (MESH:D005231), T3 (MESH:D014284), SCFAs (MESH:D005232), ROS (MESH:D017382), glucose (MESH:D005947), fructose (MESH:D005632), LPS (MESH:D008070), CY (MESH:D003545), lipid (MESH:D008055), Cortisol (MESH:D006854), vitamin E (MESH:D014810), lactose (MESH:D007785), lactate (MESH:D019344), TCA (MESH:D014233), epinephrine (MESH:D004837), Linoleic acid (MESH:D019787), Fat (MESH:D005223), water (MESH:D014867), NEFA (MESH:D005230), iron (MESH:D007501)
- **Species:** Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Staphylococcus aureus (species) [taxon 1280], Bos taurus (bovine, species) [taxon 9913], Prevotella (genus) [taxon 838], Lactobacillus (genus) [taxon 1578], Escherichia coli (E. coli, species) [taxon 562], Streptococcus pneumoniae (species) [taxon 1313], Mycoplasma (genus) [taxon 2093]

## Full text

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## Figures

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## References

213 references — full list in the complete paper: https://tomesphere.com/paper/PMC12935683/full.md

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Source: https://tomesphere.com/paper/PMC12935683