Episodic Aspiration with Oral Commensals Induces a MyD88-dependent, Pulmonary T-Helper Cell Type 17 Response that Mitigates Susceptibility to Streptococcus pneumoniae

• DOI: 10.1164/rccm.202005-1596oc
• Publication Date: 2020-11-09T22:32:36Z
• Authors: Benjamin G. Wu; Imran Sulaiman; Jun-Chieh J. Tsay; Luisanny Perez; Brendan Franca; Yonghua Li; Jing Wang; Amber N. Gonzalez; Mariam El-Ashmawy; Joseph Carpenito; Evan Olsen; Maya Sauthoff; Kevin Yie; Xiuxiu Liu; Nan Shen; Jose C. Clemente; Bianca Kapoor; Tonia Zangari; Valeria Mezzano; Cynthia Loomis; Michael D. Weiden; Sergei B. Koralov; Jeanine D’Armiento; Sunil K. Ahuja; Xue-Ru Wu; Jeffrey N. Weiser; Leopoldo N. Segal
• Keywords: Commensalism; Dysbiosis

Rationale: Cross-sectional human data suggest that enrichment of oral anaerobic bacteria in the lung is associated with an increased T-helper cell type 17 (Th17) inflammatory phenotype.Objectives: In this study, we evaluated microbial and host immune-response dynamics after aspiration commensals using a preclinical mouse model.Methods: Aspiration mixture (MOC; Prevotella melaninogenica, Veillonella parvula, Streptococcus mitis) was modeled mice followed by variable time killing. The genetic backgrounds included wild-type, MyD88-knockout, STAT3C backgrounds.Measurements Main Results: 16S-rRNA gene sequencing characterized changes microbiota. Flow cytometry, cytokine measurement via Luminex RNA host-transcriptome used to characterize immune phenotype. Although MOC correlated lower-airway dysbiosis resolved within 5 days, it induced extended response IL-17-producing T cells lasting at least 14 days. MyD88 expression required for IL-17 aspiration, but not T-cell activation or IFN-γ expression. before respiratory challenge S. pneumoniae led decrease hosts' susceptibility pathogen.Conclusions: Thus, otherwise healthy mice, single event rapidly cleared from lower airways induces prolonged Th17 secondarily decreases pneumoniae. Translationally, these implicate immunoprotective role episodic microaspiration microbes regulation phenotype mitigation infection pathogens.