NK cells contribute to persistent airway inflammation and AHR during the later stage of RSV infection in mice

Abstract

RSV can lead to persistent airway inflammation and AHR and is intimately associated with childhood recurrent wheezing and asthma, but the underlying mechanisms remain unclear. There are high numbers of NK cells in the lung, which not only play important roles in the acute stage of RSV infection, but also are pivotal in regulating the pathogenesis of asthma. Therefore, in this study, we assumed that NK cells might contribute to persistent airway disease during the later stage of RSV infection. Mice were killed at serial time points after RSV infection to collect samples. Leukocytes in bronchoalveolar lavage fluid (BALF) were counted, lung histopathology was examined, and airway hyperresponsiveness (AHR) was measured by whole-body plethysmography. Cytokines were detected by ELISA, and NK cells were determined by flow cytometry. Rabbit anti-mouse asialo-GM-1 antibodies and resveratrol were used to deplete or suppress NK cells. Inflammatory cells in BALF, lung tissue damage and AHR were persistent for 60 days post-RSV infection. Type 2 cytokines and NK cells were significantly increased during the later stage of infection. When NK cells were decreased by the antibodies or resveratrol, type 2 cytokines, the persistent airway inflammation and AHR were all markedly reduced. NK cells can contribute to the RSV-associated persistent airway inflammation and AHR at least partially by promoting type 2 cytokines. Therefore, therapeutic targeting of NK cells may provide a novel approach to alleviating the recurrent wheezing subsequent to RSV infection.

Aryl hydrocarbon receptor and intestinal immunity

“…However, other studies have shown that, unlike AhR protein expression, which is decreased in inflamed CD tissues, there is no difference in AhR gene expression between tissues from CD patients and healthy controls. 149 The involvement of post-transcriptional mechanisms may explain the disparity between AhR gene and protein expression. This is consistent with a study showing that miRNA-124, which is involved in post-ranscriptional gene regulation and had been shown to have a pro-inflammatory role in TNBS-induced colitis by suppressing AhR, is highly expressed in inflamed biopsies and IECs from CD patients.…”

Innate lymphoid cells in lung infection and immunity

“…Viral‐induced type 2 inflammation has also been observed in other pulmonary viral infections such as those caused by RSV or rhinovirus (RV) . Severe primary infections with RSV or RV during infancy are generally associated with a development of allergy and asthma later in life, as well as with severe and life‐threatening exacerbations in adult patients suffering from chronic obstructive disease (COPD), pneumonia or asthma .…”

LPS aggravates lung inflammation induced by RSV by promoting the ERK-MMP-12 signaling pathway in mice

“…The single cell suspensions of mouse lung tissue were prepared as described previously [9]. Samples were blocked with rat serum for 20 min, and then immunostained with antibody to mouse CD45, CD3, CD49b, CD19, F4/80, CD11c, CD11b, Ly6G, Ly6C or isotype control conjugated with PerCP-cy7, PerCP-cy5.5, PE, FITC or APC for 30 min on ice.…”

“…Both epidemiological studies and animal experiments have demonstrated that exposure to LPS can sensitize or exacerbate COPD and asthma by promoting Th2 responses [8]. We have identified that a Th2 cytokines-dominant airway microenvironment similar to asthma was triggered during the later stage of RSV infection [9]. However, it's not clear whether inhalation of LPS might boost RSV-associated airway inflammation and AHR by increasing Th2 responses.…”