Humoral immune responses during asthma and influenza co-morbidity in mice

Abstract

Humoral immunity serve dual functions of direct pathogen neutralization and enhancement of leukocyte function. Antibody classes are determined by antigen triggers, and the resulting antibodies can contribute to disease pathogenesis and host defense. Although asthma and influenza are immunologically distinct diseases, since we have found that allergic asthma exacerbation promotes antiviral host responses to influenza A virus, we hypothesized that humoral immunity may contribute to allergic host protection during influenza. C57BL/6J mice sensitized and challenged with Aspergillus fumigatus (or not) were infected with pandemic influenza A/CA/04/2009 virus. Negative control groups included naïve mice, and mice with only ‘asthma’ or influenza. Concentrations of antibodies were quantified by ELISA, and in situ localization of IgA- and IgE-positive cells in the lungs was determined by immunohistochemistry. The number and phenotype of B cells in spleens and mediastinal lymph nodes were determined by flow cytometry at predetermined timepoints after virus infection until viral clearance. Mucosal and systemic antibodies remained elevated in mice with asthma and influenza with prominent production of IgE and IgA compared to influenza-only controls. B cell expansion was prominent in the mediastinal lymph nodes of allergic mice during influenza where most cells produced IgG1 and IgA. Although allergy-skewed B cell responses dominated in mice with allergic airways inflammation during influenza virus infection, virus-specific antibodies were also induced. Future studies are required to identify the mechanisms involved with B cell activation and function in allergic hosts facing respiratory viral infections.

The Role of Innate Leukocytes during Influenza Virus Infection

“…During IAV infection, pDCs induce differentiation of B cells into antibody-secreting plasma cells through IFN α and IL-6 [142] and the depletion of pDCs abrogates antibody secretion [127]. The activation of lung-resident B cells during pH1N1 infection [143] may be led by these DC subsets that encounter viral antigen thereby providing dual protection at the site of infection as well as by couriering a call for help (Figure 2).…”

Influenza in Asthmatics: For Better or for Worse?

“…While total B cell numbers in the pulmonary mucosa are similar between allergic and non-allergic mice after pH1N1 infection ( 158 ), allergy-specific antibodies dominate over anti-influenza antibodies in the serum and mucosa of allergen-exposed pH1N1-infected mice ( 170 ) suggesting that pre-existing allergy does not readily promote antiviral humoral immune responses (Figure 5 ). B cell populations in lymphoid organs were not markedly different between virus-infected mice with/without allergic airways disease, however, antibody producing B cells in the lungs were elevated in co-morbid mice ( 170 ) indicating the importance of in situ mucosal immune responses in pulmonary co-morbidity. Therefore, examining the development and function of B cell responses during asthma and influenza co-morbidity may help to delineate effective vaccination strategies for patients with underlying chronic lung diseases.…”

C3: connect separate connected components to form a succinct disease module

“…Here we focused on the function annotations of GO terms (BP) and KEGG pathway. We found that C3 proteins enrichment in some pathways has a lower p value, which has been reported to be associated with asthma (PMID), such as: neuropeptide Y may promote TH2 inflammatory response in asthma [28], signal transduction of IL-13 plays a role in the pathogenesis of bronchial asthma [29], humoral immune responses during asthma [30]. And in Table 2, we present in detail the enrichment function and enriched C3 genes as well as the PMID verified by the literature.…”