Dysbiosis of intestinal microbiota increases mortality to a respiratory viral infection through elevated production of IFNγ by innate lymphoid cells
Monday, March 5, 2018
South Hall A2 (Convention Center)
Syed-Rehan A Hussain, PhD, Jennifer L Santoro, Michelle Rohlfing, Nita H. Salzman, MD PhD, Mitchell H. Grayson, MD FAAAAI
RATIONALE: Using a normally non-lethal dose of Sendai virus (SeV), we demonstrated that alteration of just the intestinal microbiota led to a marked and significant increase in mortality. The mechanism of this increased mortality was due to dysregulation of IFNγ production in the lung, although the cellular source responsible for the increased IFNγ production was unclear. One source of IFNγ is innate lymphoid cells (ILCs), which unlike T-helper (Th) cells, lack surface antigen receptors. This study investigated the role of lung ILCs in increased IFNγ production during a SeV infection and intestinal microbiota dysbiosis.

METHODS: C57BL/6 mice were given reverse osmosis drinking water with or without the non-absorbable antibiotic, streptomycin (0.5 g/250 ml). After 2 weeks mice were intranasally inoculated with 30 μl of 2 x105 plaque forming units of SeV. On day 8 post infection lung cells were harvested. ILC’s were identified by flow cytometry as being Lin- CD4+ lymphocytes, with intracellular staining used to determine IFNγ levels.

RESULTS: ILCs represented 5.1+/-0.6% (mean+/-SEM) of the lymphoid cells in the murine lung during SeV infection, and this was not altered by streptomycin treatment (4.3+/-0.4%, p=0.3, n=5). Similarly, the absolute numbers of ILCs was not affected by antibiotic treatment (p=0.2). However, the frequency of IFNγ producing ILCs increased from 0.90+/-0.4% to 2.85+/-0.6% with streptomycin treatment (p=0.04, n=4).

CONCLUSIONS: ILCs, while being a small population, may represent the cell type that is responsible for increased pulmonary IFNγ during a respiratory viral infection after disruption of gastrointestinal microbiota.