Maternal smoking during pregnancy and exposure of infants to cigarette smoke are strongly associated with adverse health effects in childhood including higher susceptibility to respiratory viral infections. Human respiratory syncytial virus (HRSV) is the most important cause of lower respiratory tract infection among young infants. Exacerbation of respiratory disease, including HRSV bronchiolitis and higher susceptibility to HRSV infection, is well correlated with previous smoke exposure. The mechanisms of recurrence and susceptibility to viral pathogens after passive smoke exposure are multifactorial and include alteration of the structural and immunologic host defenses. In this work, we used a well-established mouse model of in utero smoke exposure to investigate the effect of in utero smoke exposure in HRSV-induced pathogenesis. Sample analysis indicated that in utero exposure led to increased lung inflammation characterized by an increased influx of neutrophils to the airways of the infected mice and a delayed viral clearance. On the other hand, decreased HRSV-specific CD8+ T-cell response was observed. These findings indicate that cigarette smoke exposure during pregnancy alters HRSV-induced disease as well as several aspects of the neonatal immune responses.

Human Metapneumovirus (HMPV) remains one of the most common viral infections causing acute respiratory tract infections, especially in young children, elderly, and immunocompromised populations. Clinical symptoms can range from mild respiratory symptoms to severe bronchiolitis and pneumonia. The production of mucus is a common feature during HMPV infection, but its contribution to HMPV-induced pathogenesis and immune response is largely unknown. Mucins are a major component of mucus and they could have an impact on how the host responds to infections. Using an in vitro system and a mouse model of infection, we identified that Mucin 19 is predominantly expressed in the respiratory tract upon HMPV infection. Moreover, the lack of Muc19 led to an improved disease, lower lung viral titers and a decrease in the number of CD4+ T cells. These data indicate that mucin 19 contributes to the activation of the immune response to HMPV and to HMPV-induced pathogenesis.

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Human metapneumovirus (HMPV) is a negative sense, single stranded RNA virus that belongs to the Pneumovirdae family, and represents an important pathogen that causes severe bronchiolitis and pneumonia worldwide. There is currently no vaccine against this virus, so it is important to study the aspects of the immune response induced by HMPV in order to understand its mechanism of infection. Because infiltration of mucus is a hallmark of HMPV infection, it is warranted to study the role of mucus in the disease process. Mucin proteins make up the major component of mucus and can be found within the airway and lungs. Using an in vitro model of HMPV infection and human bronchial epithelial cells, we found that HMPV induced predominantly a mucin 19 expression. Those data were confirmed in mice, where HMPV induced predominant levels of muc19 protein. Mucin 19 is a secreted gel-forming mucin, whose function is largely understudied, particularly in the respiratory tract. Our findings led us to hypothesize that mucin 19 plays a role in HMPV infection. To test that, we used a muc19 knockout mouse model. Lung samples were collected at different time points. Sample analysis showed that the absence of muc19 led to an increased pulmonary inflammation and body weight loss. Interestingly, flow cytometry data indicate that the lack of Muc19 resulted in a decreased CD4+ T cell count in the lung, and reduced numbers of CD4+ and CD8+ T cells in the lymph nodes after HMPV infection. These novel findings yield relevant information regarding the contribution of the mucins, specifically Muc19, on the immune response induced by respiratory viral infections in the lung.