Heat shock suppresses the innate immune response of bovine endometrial epithelial cells

With rising global temperatures, it is imperative to determine the impact of heat stress on the physiology of food-producing animals. Dairy cows are susceptible to uterine diseases that reduce fertility. Immune function is important in the development and progression of disease; however, the effect of heat shock on the innate immune capacity of endometrial epithelial cells remains underexplored. Here, we investigated how heat shock alters the innate immune response and mitochondrial respiration of bovine endometrial epithelial cells. Primary endometrial epithelial cells were collected from postpartum cows and cultured in the presence of lipopolysaccharide under thermoneutral (38.5°C) or heat shock (40.0°C) conditions. Time-course and sequential heat shock experiments were conducted to assess gene expression dynamics of HSPA1A, TLR4, CXCL8, IL6, and IL1B. Cell viability was evaluated by MTT assay, and mitochondrial respiration was analyzed using high-resolution respirometry. Heat shock did not affect cell viability or overall mitochondrial respiration but reduced proton leak-related oxygen consumption. Acute heat shock induced HSPA1A expression but suppressed LPS-stimulated CXCL8 and IL6 expression. Expression of TLR4 increased when cells were recovering from heat shock or following sequential heat shock. Sequential heat shock did not affect the expression of pro-inflammatory mediators compared to a single heat shock event. In conclusion, acute heat shock of bovine endometrial epithelial cells reduced the innate immune response to LPS without impacting cell viability or mitochondrial function. Altered endometrial immune function may contribute to the increased incidence of uterine diseases in cows under heat stress conditions.

As global temperatures continue to rise, food-producing animals face increasing challenges to their fertility and productivity. Uterine disease in dairy cows reduces fertility and impacts milk production. Heat stress is known to disrupt immune function, but less is understood about how elevated temperatures affect the cells that line the uterus that respond to invading pathogens. We examined how acute heat exposure affects the immune response of uterine cells to respond to pathogens and found that heat shock reduces their ability to produce key immune molecules needed to fight bacteria. This suggests that heat stress directly weakens the natural defenses of the uterus and helps us understand why cows are vulnerable to reproductive diseases during hot weather. Understanding these effects can guide better management strategies to protect animal health in a warming climate.