IL17-Producing γδ T Cells May Enhance Humoral Immunity during Pulmonary Pseudomonas aeruginosa Infection in Mice

Abstract

The host acquired immune response, especially the humoral immunity, plays key roles in preventing bacterial pneumonia in the lung. Our previous research demonstrated that interleukin 17-producing γδ T cells (IL17-γδ T cells) have a protective effect on the early innate immune response during acute pulmonary Pseudomonas aeruginosa infection. However, whether IL17-γδ T cells also play a role in humoral immunity is unknown. In this study, an acute pulmonary P. aeruginosa infection model was established in wild-type and γδ TCR−/− C57BL/6 mice. The expression of IL-17 on γδ T cells isolated from infected lung tissues increased rapidly and peaked at day 7 after acute infection with P. aeruginosa. Compared with wild-type infected mice, the levels of total immunoglobulins including IgA, IgG, and IgM in the serum and BALF were significantly decreased in γδ TCR−/− mice, with the exception of IgM in the BALF. Moreover, CD69 expression in B cells from the lungs and spleen and the level of BAFF in the plasma were also decreased in γδ TCR−/− mice. IL17-γδ T cell transfusion significantly improved the production of immunoglobulins, B cell activation and BAFF levels in γδ TCR−/− mice compared with γδ TCR−/− mice without transfusion; this effect was blocked when cells were pretreated with an IL-17 antibody. Together, these data demonstrate that IL17-γδ T cells are involved in CD19+ B cell activation and the production of immunoglobulins during acute pulmonary P. aeruginosa infection. Thus, we conclude that IL17-γδ T cells may facilitate the elimination of bacteria and improve survival through not only innate immunity but also humoral immunity.

A live auxotrophic vaccine confers mucosal immunity and protection against lethal pneumonia caused by Pseudomonas aeruginosa

“…Numerous studies have shown a host protective role of IL-17A in PA pneumonia [21,36,37]. IL-17-producing γδ T cells have been shown to promote neutrophil chemotaxis, eliminating PA bacteria during acute pulmonary infection [38] and to be involved in B cell activation [39]. However, our results appear to indicate that CD4 + T helper cells, rather than γδ T cells are stimulated by the α-PA vaccine to produce IL-17A as the IN-immunized mice presented increased frequencies of IL-17A + CD4 + cells in lungs than controls, while IL-17-producing γδ T cells were found at similar frequencies in both groups.…”

Immunization with Bivalent Flagellin Protects Mice against FatalPseudomonas aeruginosaPneumonia

“…A recent study has shown that γδ T cells produced IL-17 in the lungs as early as 2 h after Bordetella pertussis infection [ 43 ]. The level of IL-17 increased 6 h after infection, demonstrating that acute pulmonary infection with P. aeruginosa rapidly induced IL-17 production in the lungs; this IL-17 may be involved in the innate immune response to the infection [ 44 , 45 ].…”

Mechanisms and Targeted Therapies forPseudomonas aeruginosaLung Infection

“…In a murine model of P. aeruginosa lung infection, IL-17-producing gd T cells were found to be essential for B-cell production of antibodies detected in serum and bronchial lavage fluid (165). An additional model demonstrated that B cells also produced IL-17, but in mice lacking B cells (mMT mice), pathogenesis was not affected (166), which highlights the lack of target specificity of the antibodies generated.…”