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

• Published in: PloS one Vol. 15; no. 5; p. e0226539
• Main Authors: Belay, Tesfaye, Martin, Elisha, Brown, Gezelle, Crenshaw, Raenel, Street, Julia, Freeman, Ashleigh, Musick, Shane, Kinder, Tyler J.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.05.2020; Public Library of Science (PLoS)
• Subjects: Adrenergic beta-Agonists - pharmacology; Adrenergic beta-Antagonists - pharmacology; Adrenergic receptors; Animal models; Animals; Biological response modifiers; Biology and Life Sciences; Body temperature changes; Bone marrow; CD4 antigen; Cells, Cultured; Chlamydia; Chlamydia infections; Chlamydia Infections - immunology; Chlamydia muridarum; Cold; Cold effects; Cold-Shock Response; Cytokines; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Development and progression; Differentiation; DNA binding proteins; Female; Fenoterol; Fenoterol - pharmacology; GATA-3 protein; Health aspects; Heat/cold application; Human subjects; Immune response; Immune system; Immunologic research; Infection; Infections; Infertility; Interferon; Interferon-gamma - genetics; Interferon-gamma - metabolism; Interleukin 10; Interleukin 23; Interleukin 4; Interleukins; Interleukins - genetics; Interleukins - metabolism; Laboratory animals; Low level; Lymphocytes; Lymphocytes T; Medicine and Health Sciences; Messenger RNA; Mice; Mice, Inbred BALB C; Physical Sciences; Physiological aspects; Propanolamines - pharmacology; Receptors; Receptors, Adrenergic, beta - genetics; Receptors, Adrenergic, beta - metabolism; Research and Analysis Methods; RNA; Sexually transmitted diseases; Socioeconomic factors; Spleen; STD; Stimulation; Stress; Stress (Physiology); Subpopulations; T cells; T-bet Transcription Factor; T-Box Domain Proteins - genetics; T-Box Domain Proteins - metabolism; Th1 Cells - drug effects; Th1 Cells - immunology; Th2 Cells - drug effects; Th2 Cells - immunology; Time; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Urogenital diseases; Water treatment; γ-Interferon; United States; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0226539

A murine model to study the effect of cold-induced stress (CIS) on Chlamydia muridarum genital infection and immune response has been developed in our laboratory. Previous results in the lab show that CIS increases the intensity of chlamydia genital infection, but little is known about the effects and mechanisms of CIS on the differentiation and activities of CD4+ 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 are not well defined. In this study, we examined whether CIS modulates the expressions of beta-adrenergic receptor (β-AR), transcription factors, hallmark cytokines of Th1 and Th2, and differentiation of BMDCs during C. muridarum genital infection in the murine model. Our results show that the mRNA level of the beta2-adrenergic receptor (β2-AR) compared to β1-AR and β3-AR was high in the mixed populations of CD4+ T cells and BMDCs. Furthermore, we observed decreased expression of T-bet, low level of Interferon-gamma (IFN-γ) production, increased expression of GATA-3, and Interleukin-4 (IL-4) production in CD4+ T cells of stressed mice. Exposure of BMDCs to Fenoterol, β2-AR agonist, or ICI118,551, β2-AR antagonist, revealed significant β2-AR stimulation or inhibition, respectively, in stressed mice. Moreover, co-culturing of mature BMDCs and naïve CD4+ T cells increased the production of IL-4, IL-10, L-17, and IL-23 cytokines, suggesting that stimulation of β2-AR leads to the increased production of Th2 cytokines. Overall, our results show for the first time that CIS promotes the switching from a Th1 to Th2 cytokine environment. This was evidenced in the murine stress model by the overexpression of GATA-3 concurrent with elevated IL-4 production, reduced T-bet expression, and IFN-γ secretion.