Year-end Sale % OFF 
Abstract
The role of interleukin-22 (IL-22) in intracellular bacterial infections is a controversial issue, although the contribution of this cytokine to host defense against extracellular bacterial pathogens has been well established. In this study, we focused on an intra-cellular bacterium, Chlamydia, and evaluated the production and function of IL-22 in host defense against chlamydial lung infection using a mouse model. We found that Chlamydia muridarum infection elicited quick IL-22 responses in the lung, which increased during infection and were reduced when bacterial loads decreased. More importantly, blockade of endogenous IL-22 using neutralizing anti-IL-22 monoclonal antibodies (mAb) resulted in more severe disease in the mice, leading to significantly higher weight loss and bacterial growth and much more severe pathological changes than treatment with isotype control antibody. Immunological analyses identified significantly lower T helper 1 (Th1) and Th17 responses in the IL-22-neutralized mice. In contrast, intranasal administration of exogenous IL-22 significantly enhanced protection following chlamydial lung infection, which was associated with a significant increase of Th17 response. The data demonstrate that IL-22 is a critical cytokine, mediating host defense against chlamydial lung infection and coordinating the function of distinct Th-cell subsets, particularly Th1 and Th17, in the process.
Highlights
As a member of the interleukin-10 (IL-10) family, IL-22 is an important cytokine for modulating inflammatory responses [1]
The results demonstrate that Chlamydia muridarum (Cm) lung infection induces a quick IL-22 response, suggesting that it might be involved in host defense against the infection
We found that lung, spleen and draining lymph node (LN) cells isolated from IL-22–neutralized mice produced significantly lower levels of IL-17/T helper 17 (Th17)-promoting cytokine (IL-6) and higher levels of transforming growth factor-β (TGF-β) than isotype control mice (Figures 3F–H)
Summary
As a member of the interleukin-10 (IL-10) family, IL-22 is an important cytokine for modulating inflammatory responses [1]. IL-22 can be produced by innate and adaptive immune cell populations, most notably T helper 17 (Th17) cells, and γδ T cells, natural killer T cells (NKT cells), lymphoid tissue inducer (LTi) cells, and LTi-like cells [2,3]. IL-22 targets to various tissues, including the lung, gut, skin, liver, pancreas and kidney, for biological function [4,5,6]. The reported biological functions of IL-22 include upregulation of antimicrobial proteins and enhancement of regeneration and innate immunity [4,5,6]. It is generally accepted that IL-22 plays a protective role in extracellular bacterial infections, such as Citrobactor rodentium [6], Klebsiella pneumoniae [7] and segmented filamentous bacterium (SFB)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
