Vaccination modulates pulmonary eosinophil subsets upon breakthrough influenza infection.

Abstract

Abstract Eosinophils play a critical role in mucosal tissue homeostasis, anti-helminth responses, and allergy. Lung eosinophilia is associated with aberrant T cell responses to respiratory viral infection and is also a consequence of vaccine-associated enhanced respiratory disease (VAERD). A growing body of literature has demonstrated there are different phenotypic subsets of eosinophils and, depending on subset, can play a protective role and aid in lung recovery following infection. Previous work by Choi et al. showed recruitment of eosinophils to the lung in BALB/c mice vaccinated with alum-adjuvanted trivalent inactivated influenza vaccine (TIV) following a sub-lethal H1N1 (A/New Caledonia/20/1999; NC99) influenza challenge. In this study, flow cytometric analysis of the lung showed an increase in total lung eosinophil numbers in all NC99-challenged mice compared to controls. Furthermore, in TIV-vaccinated then challenged mice, flux of inflammatory eosinophil (iEos) and resident eosinophil (rEos) numbers at 7 days post-infection (DPI) resulted in iEos/rEos ratios similar to that of OVA-sensitized allergic control mice; this effect was independent of alum adjuvant. Treatment groups with increased lung eosinophil numbers did not show signs of enhanced morbidity or inflammatory cytokine signatures compared to unvaccinated mice. Unsupervised clustering using CATALYST confirmed findings from manual gating analysis and revealed differences in eosinophil activation status based on surface expression levels of MHC Class II. Our findings provide a starting point for more sophisticated phenotypic characterization of eosinophil subsets and their distinct functional contributions to vaccine- and infection-induced immunity. This research was partly funded by NIAID T32 Virus-Host Interactions Training Grant (5T32AI007647-22) and CRIP (Center for Research for Influenza Pathogenesis), a NIAID supported Center of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C).