Chronic heat stress delays immune system development and alters serotonin signaling in pre-weaned dairy calves

Exposure to heat stress can alter the development and immune system function in dairy calves. Serotonin is an immunomodulatory biogenic amine that functions as a neurotransmitter and as a stress-response mediator. Our objectives were to characterize the patterns of serum serotonin concentrations and the pattern of serotonin-related genes expressed by immune cells of calves exposed to chronic heat stress or heat stress abatement during early life, and to explore whether these might relate to immune system development. Dairy calves were exposed to chronic heat stress (HS; n = 6) or heat stress abatement (cooling, CL; n = 6) across the prenatal (late gestation, last 46 d) and postnatal (from birth to weaning, 56 d) developmental windows. Blood samples were collected to harvest serum (weekly, from d 1 to 49), to isolate of circulating leukocyte mRNA (at 1, 21 and 42 d of age) and characterize immune cell populations by flow cytometry (at 21 and 47 d of age). Calves exposed to chronic heat stress pre- and postnatally had lower red blood cell counts and lower circulating serotonin, immunoglobulin G, and B-lymphocytes compared to CL calves. Circulating blood leukocyte mRNA expression of serotonin receptors -1A, -1F, -4 and -5 was greater, while heat shock protein 70 and immune-related genes (i.e., TBX21, TLR4, and TGFβ) were lower in HS relative to CL calves. Peripheral blood leukocytes from all calves secreted serotonin and interleukin-6 after in-vitro lipopolysaccharide stimulation. However, the HS calves produced more serotonin and less interleukin-6 than CL calves when activated in-vitro. Together, our data suggest that providing heat stress abatement to dairy calves across prenatal and postnatal developmental windows might modulate the serotonin synthesis pathway in ways that may benefit humoral immunity against microbial pathogens.