IL-23-dependent IL-17 production is essential in neutrophil recruitment and activity in mouse lung defense against respiratory Mycoplasma pneumoniae infection.
IL-23 induces IL-17 production in activated CD4+ T cells and participates in host defense against many encapsulated bacteria. However, whether the IL-23/IL-17 axis contributes to a Mycoplasma pneumoniae (Mp)-induced lung inflammation (e.g., neutrophils) has not been addressed. Using an acute respiratory Mp infection murine model, we found significantly up-regulated lung IL-23p19 mRNA in the early phase of infection (4h), and alveolar macrophages were an important cell source of Mp-induced IL-23. We further showed that Mp significantly increased IL-17 protein levels in bronchoalveolar lavage (BAL). Lung gene expression of IL-17, IL-17C and IL-17F was also markedly up-regulated by Mp in vivo. IL-17 and IL-17F were found to be derived mainly from lung CD4+ T cells, and were increased upon IL-23 stimulation in vitro. In vivo blocking of IL-23p19 alone or in combination with IL-23/IL-12p40 resulted in a significant reduction of Mp-induced IL-17 protein and IL-17/IL-17F mRNA expression, which was accompanied by a trend toward reduced lung neutrophil recruitment, BAL neutrophil activity, and Mp clearance. However, IL-23 neutralization had no effect on Mp-induced lung IL-17C mRNA expression. These results demonstrate that IL-17/IL-17F production is IL-23-dependent in an acute Mp infection, and contributes to neutrophil recruitment and activity in the lung defense against the infection.
Wu
Qun
Q
Department of Medicine, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, CO 80206, USA.
Martin
Richard J
RJ
Rino
John G
JG
Breed
Rachel
R
Torres
Raul M
RM
Chu
Hong Wei
HW
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000382:microbiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D005260:Female; D053762:Interleukin-12 Subunit p40 / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D053759:Interleukin-23 / Q000276:immunology*; D053760:Interleukin-23 Subunit p19 / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000382:microbiology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009177:Mycoplasma pneumoniae / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D011019:Pneumonia, Mycoplasma / Q000276:immunology* / Q000382:microbiology
D053762:Interleukin-12 Subunit p40; D020381:Interleukin-17; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19