Erika Buell

CD49d-expressing neutrophils differentiate atopic from nonatopic individuals

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Characterization of Intestinal Dendritic Cells in Murine Norovirus Infection

We have shown that respiratory viral infections drive allergic disease through dendritic cells, whether gastrointestinal viruses induce allergies is not known. Norovirus infections are a major cause of gastroenteritis in humans. We used murine norovirus (MNV) to explore the effect of MNV infection on gastrointestinal conventional DCs (cDCs) and plasmacytoid DCs (pDCs). MNV infection induced disparate effects on cDCs and pDCs in lymphoid tissues of the small intestine and draining mesenteric lymph nodes. FcεRI was transiently expressed on lamina propria cDCs, but not on pDCs. In addition, feeding ovalbumin during the viral infection led to a modest, brief induction of anti-ovalbumin IgE. Together, these data suggest that like with a respiratory viral infection, an intestinal viral infection may be sufficient to induce changes in DCs and the generation of food-specific IgE. Whether this represents a novel mechanism of food allergy remains to be determined.

CysLTR1-expression identifies a subset of neutrophils during the antiviral response that contributes to post-viral atopic airway disease

Background Viral respiratory tract infections increase the risk of development and exacerbation of atopic disease. Previously, we demonstrated the requirement for a neutrophil (PMN) subset expressing CD49d to drive development of postviral atopic airway disease in mice. Objective We sought to determine whether human CD49d+ PMNs are present in the nasal mucosa during acute viral respiratory tract infections and further characterize this PMN subset in human subjects and mice. Methods Sixty subjects (5‐50 years old) were enrolled within 4 days of acute onset of upper respiratory symptoms. Nasal lavage for flow cytometry and nasal swabs for viral PCR were performed at enrollment and during convalescence. The Sendai virus mouse model was used to investigate the phenotype and functional relevance of CD49d+ PMNs. Results CD49d+ PMN frequency was significantly higher in nasal lavage fluid during acute respiratory symptoms in all subjects (2.9% vs 1.0%, n = 42, P < .001). In mice CD49d+ PMNs represented a “proatopic” neutrophil subset that expressed cysteinyl leukotriene receptor 1 (CysLTR1) and produced TNF, CCL2, and CCL5. Inhibition of CysLTR1 signaling in the first days of a viral respiratory tract infection was sufficient to reduce accumulation of CD49d+ PMNs in the lungs and development of postviral atopic airway disease. Similar to the mouse, human CD49d+ PMNs isolated from nasal lavage fluid during a viral respiratory tract infection expressed CysLTR1. Conclusion CD49d and CysLTR1–coexpressing PMNs are present during symptoms of an acute viral respiratory tract infection in human subjects. Further study is needed to examine selective targeting of proatopic neutrophils as a potential therapeutic strategy to prevent development of postviral atopic airway disease. Graphical abstract Figure. No Caption available.