Role of gamma-delta T cells in host response against Staphylococcus aureus-induced pneumonia

Abstract

BackgroundStaphylococcus aureus is the major cause of hospital-acquired and community-acquired pneumonia. Host defense to S.aureus infection is largely mediated by the innate immune system. γδ T cells play an important role in innate immunity to many infectious diseases. However, less is known about the role of these cells during S.aureus-induced pneumonia. In this study, we examined the response and the role of γδ T cells to pulmonary S.aureus infection.ResultsMice infected with S. aureus intranasally showed rapid γδ T cells accumulation in the lung. Deficiency of γδ T cells led to attenuated bacterial clearance and less tissue damage in lung compared with WT mice. Moreover, TCR-δ−/− mice exhibited impaired neutrophil recruitment and reduced cytokine production at the site of infection. The γδ T cells in response to pulmonary S. aureus infection mainly secreted IL-17 and γδ T cells deficiency reduced IL-17 production, which might regulate the production of neutrophil-inducing cytokine/chemokine in the S. aureus-infected lungs.ConclusionsAccumulation of γδ T cells in the lungs to S. aureus infection is beneficial for bacteria clearance and also contributes to the tissue damage. These cells were the primary source of IL-17, which might influence the recruitment of neutrophils at the early stage of infection.

Nlrp-3-Driven Interleukin 17 Production by γδT Cells Controls Infection Outcomes during Staphylococcus aureus Surgical Site Infection

“…Given that IL-17 has been identified as an important correlate of immune protection during S. aureus infection (13), it is vital that the unique cellular sources of this cytokine and mechanisms inducing its activation are identified at distinct sites of infection. Our data support recent murine model studies that suggest ␥␦T cells are a more important source of IL-17 during S. aureus infection than Th17 cells (21,22). Furthermore, our study demonstrates that while IL-17 may be critically important for mediating immune protection during S. aureus infection through this cytokine's well-documented ability to modulate downstream phagocytic cell functions (42), the relative contribution of ␥␦T cells to these protective effects may be critically dependent upon the capacities of individual strains to activate IL-1␤ production.…”

“…More recently it was shown that impaired bacterial clearance in ␦TCR Ϫ/Ϫ mice was associated with reduced IL-17 production (21), with IL-17 shown to be critical for the recruitment of neutrophils to the site of skin infection. Similarly, during S. aureusinduced pneumonia, local IL-17 production in the lung was significantly reduced in the absence of ␥␦T cells, and this was associated with impaired neutrophil recruitment and elevated bacterial burden in the lungs of ␦TCR Ϫ/Ϫ mice compared to wildtype mice (22). Taken together, these studies suggest that ␥␦T cells, as opposed to Th17 cells, are the more important source of IL-17 during S. aureus infection and support further investigation of their role in infection at alternative nonmucosal sites.…”

Identification of Immune Effectors Essential to the Control of Primary and Secondary Intranasal Infection with Brucella melitensis in Mice

“…However, we observed that TCR-d and TAP1 deficiency, but not MHCII deficiency, also affected early Brucella control in the lungs, suggesting that these cells could be a potential source of IL-17A in our model. In keeping with this observation, IL-17 production by g/d T cells was reported in a Brucella model (65) and in several other pulmonary infectious models (66)(67)(68).…”

Chlorine gas exposure increases susceptibility to invasive lung fungal infection

“…Collectively, the lack of robust IL-17A and IL-22 production in the lungs of Cl 2 -exposed mice after microbial challenge suggests that a component of Cl 2 -induced immunosuppression is lower induction of soluble antimicrobial factors via the IL-17A and IL-22 axis. Since IL-17A and IL-22 are essential effector cytokines that coordinate the immune response to multiple lung pathogens, including A. fumigatus (26,61), influenza (33,46), Pseudomonas aeruginosa (15), Klebsiella pneumonia (4), and Staphylococcus aureus (17,32), our finding has broad implications for lung host defense mechanisms impaired by Cl 2 gas exposure (and potentially other agents that target the respiratory tract).…”