IL-21/IL-21R Signaling Aggravated Respiratory Inflammation Induced by Intracellular Bacteria through Regulation of CD4+ T Cell Subset Responses

The IL-21/IL-21R interaction plays an important role in a variety of immune diseases; however, the roles and mechanisms in intracellular bacterial infection are not fully understood. In this study, we explored the effect of IL-21/IL-21R on chlamydial respiratory tract infection using a chlamydial respiratory infection model. The results showed that the mRNA expression of IL-21 and IL-21R was increased in Chlamydia muridarum-infected mice, which suggested that IL-21 and IL-21R were involved in host defense against C. muridarum lung infection. IL-21R(-/-) mice exhibited less body weight loss, a lower bacterial burden, and milder pathological changes in the lungs than wild-type (WT) mice during C. muridarum lung infection. The absolute number and activity of CD4(+) T cells and the strength of Th1/Th17 responses in IL-21R(-/-) mice were significantly higher than those in WT mice after C. muridarum lung infection, but the Th2 response was weaker. Consistently, IL-21R(-/-) mice showed higher mRNA expression of Th1 transcription factors (T-bet/STAT4), IL-12p40, a Th17 transcription factor (STAT3), and IL-23. The mRNA expression of Th2 transcription factors (GATA3/STAT6), IL-4, IL-10, and TGF-b in IL-21R(-/-) mice was significantly lower than that in WT mice. Furthermore, the administration of recombinant mouse IL-21 aggravated chlamydial lung infection in C57BL/6 mice and reduced Th1 and Th17 responses following C. muridarum lung infection. These findings demonstrate that IL-21/IL-21R may aggravate chlamydial lung infection by inhibiting Th1 and Th17 responses.

Automated summary

The IL-21/IL-21R interaction is involved in host defense against C. muridarum lung infection, with IL-21R(-/-) mice exhibiting a stronger CD4(+) T cell response and higher Th1/Th17 cytokine levels, leading to reduced bacterial burden and milder lung pathology. Conversely, administration of recombinant mouse IL-21 worsens chlamydial lung infection by inhibiting Th1 and Th17 responses.