IL-9 blockade attenuates inflammation in a murine model of methicillin-resistant Staphylococcus aureus pneumonia.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is an important etiology of pneumonia. Interleukin (IL)-9 is a T helper 9 (Th9) cytokine and participates in the pathogenesis of infectious diseases. Here, we investigated the role of IL-9 by using an MRSA pneumonia animal model. The BALB/c mice underwent nasal inhalation with an ST239 MRSA strain to establish the mouse model of MRSA pneumonia, and a subset of mice were intravenously injected with IL-9 neutralizing antibody or immunoglobulin (Ig) G. At 3 and 8days postinfection, the peripheral blood, bronchioalveolar lavage fluid (BALF), and lung tissues were collected. The frequencies of Th9 cells and the levels of cytokines in peripheral blood, BALF, and lung tissues were determined by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. The colony counts of MRSA in BALF and lung tissue were detected. The lung pathological changes were examined using hematoxylin and eosin staining. Data from flow cytometry, qRT-PCR, and ELISA showed that MRSA-infected mice exhibited higher frequency of Th9 cells and higher IL-9 mRNA and protein levels in the peripheral blood, BALF, and lung tissues of mice. In contrast, the neutralization of IL-9 abrogated MRSA inoculation-induced Th9 cell generation and IL-9 production in BALF and lung tissues. Furthermore, bacterial counting and histological examination showed that the numbers of bacteria in BALF and lungs and the lung pathological scores induced by MRSA inoculation were attenuated by the neutralization of IL-9. Moreover, cell counting and ELISA results demonstrated that IL-9 neutralization diminished the MRSA inoculation-induced count of neutrophils and macrophages and levels of pro-inflammatory cytokines in BALF. Collectively, IL-9 neutralization attenuated inflammation of MRSA pneumonia by regulating Th9/IL-9 expression.