Modulation of T helper 1 and T helper 2 immune balance in a stress mouse model during Chlamydia muridarum genital infection

Abstract

A mouse model to study the effect of cold-induced stress on Chlamydia muridarum genital infection and immune response has been developed in our laboratory. Our previous results show that cold-induced stress increases the intensity of chlamydia genital infection, but little is known about the effect of cold-induced stress on differentiations and activities of T cell subpopulations and bone marrow derived dendritic cells (BMDCs). The factors that regulate the production of T helper 1 (Th1) or T helper 2 (Th2) cytokines is not clear. The objective of this study was to examine whether cold-induced stress modulates the expression of transcription factors and hallmark cytokines of Th1 and Th2 or differentiation of BMDCs during C. muridarum genital infection in mice. Our results show that mRNA level of beta2-adrenergic receptor ({beta}2-AR) compared to {beta}1-AR and {beta}3-AR was high in mixed population of CD4+ T cells and BMDCs. Further, decreased expression of T-bet and low level of interferon-gamma (IFN-{gamma}) production and increased expression of GATA-3 and interleukin-4 (IL-4) production in CD4+ T of stressed mice was observed. Exposure of BMDCs to feroterol ({beta}2-AR agonist) or ICI,118551 ({beta}2-AR antagonist), respectively, revealed significant stimulation or inhibition of {beta}2-AR in stressed mice. Moreover, co-culturing of mature BMDC and naive CD4+ T cells resulted in increased production of IL-4, IL-10, and IL-17 in culture supernatants, suggesting that stimulation of {beta}2-AR leads to the increased production of Th2 cytokines. Overall, our results show for the first time that cold-induced stress is able to modulate the pattern of Th1 and Th2 cytokine environment, suggesting that it promotes the differentiation to Th2 rather than Th1 by the overexpression of GATA-3 correlated with elevated production of IL-4, IL-10, IL-23, and IL-17 in contrast to a low expression of T-bet correlated with less IFN-{gamma} secretion in the mouse model.