Dataset Information

Lung ?? T Cells Mediate Protective Responses during Neonatal Influenza Infection that Are Associated with Type 2 Immunity.

ABSTRACT: Compared to adults, infants suffer higher rates of hospitalization, severe clinical complications, and mortality due to influenza infection. We found that ?? T cells protected neonatal mice against mortality during influenza infection. ?? T cell deficiency did not alter viral clearance or interferon-? production. Instead, neonatal influenza infection induced the accumulation of interleukin-17A (IL-17A)-producing ?? T cells, which was associated with IL-33 production by lung epithelial cells. Neonates lacking IL-17A-expressing ?? T cells or Il33 had higher mortality upon influenza infection. ?? T cells and IL-33 promoted lung infiltration of group 2 innate lymphoid cells and regulatory T cells, resulting in increased amphiregulin secretion and tissue repair. In influenza-infected children, IL-17A, IL-33, and amphiregulin expression were correlated, and increased IL-17A levels in nasal aspirates were associated with better clinical outcomes. Our results indicate that ?? T cells are required in influenza-infected neonates to initiate protective immunity and mediate lung homeostasis.

SUBMITTER: Guo XJ

PROVIDER: S-EPMC6345262 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Publications

Lung γδ T Cells Mediate Protective Responses during Neonatal Influenza Infection that Are Associated with Type 2 Immunity.

Guo Xi-Zhi J XJ Dash Pradyot P Crawford Jeremy Chase JC Allen E Kaitlynn EK Zamora Anthony E AE Boyd David F DF Duan Susu S Bajracharya Resha R Awad Walid A WA Apiwattanakul Nopporn N Vogel Peter P Kanneganti Thirumala-Devi TD Thomas Paul G PG

Immunity 20180828 3

Compared to adults, infants suffer higher rates of hospitalization, severe clinical complications, and mortality due to influenza infection. We found that γδ T cells protected neonatal mice against mortality during influenza infection. γδ T cell deficiency did not alter viral clearance or interferon-γ production. Instead, neonatal influenza infection induced the accumulation of interleukin-17A (IL-17A)-producing γδ T cells, which was associated with IL-33 production by lung epithelial cells. Neo ...[more]

PMID: 30170813

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Project description:Mast cells release disease-causing mediators and accumulate in the lung of asthmatics. The most common cause of exacerbations of asthma is respiratory virus infections such as influenza. Recently, we demonstrated that influenza infection in mice triggers the recruitment of mast cell progenitors to the lung. This process starts early after infection and leads to the accumulation of mast cells. Previous studies showed that an adaptive immune response was required to trigger the recruitment of mast cell progenitors to the lung in a mouse model of allergic lung inflammation. Therefore, we set out to determine whether an adaptive immune response against the virus is needed to cause the influenza-induced recruitment of mast cell progenitors to the lung. We found that influenza-induced recruitment of mast cell progenitors to the lung was intact in Rag2 -/- mice and mice depleted of CD4+ cells, implicating the involvement of innate immune signals in this process. Seven weeks after the primary infection, the influenza-exposed mice harbored more lung mast cells than unexposed mice. As innate immunity was implicated in stimulating the recruitment process, several compounds known to trigger innate immune responses were administrated intranasally to test their ability to cause an increase in lung mast cell progenitors. Poly I:C, a synthetic analog of viral dsRNA, induced a TLR3-dependent increase in lung mast cell progenitors. In addition, IL-33 induced an ST2-dependent increase in lung mast cell progenitors. In contrast, the influenza-induced recruitment of mast cell progenitors to the lung occurred independently of either TLR3 or ST2, as demonstrated using Tlr3 -/- or Il1rl1 -/- mice. Furthermore, neutralization of IL-33 in Tlr3 -/- mice could not abrogate the influenza-induced influx of mast cell progenitors to the lung. These results suggest that other innate receptor(s) contribute to mount the influx of mast cell progenitors to the lung upon influenza infection. Our study establishes that mast cell progenitors can be rapidly recruited to the lung by innate immune signals. This indicates that during life various innate stimuli of the respiratory tract trigger increases in the mast cell population within the lung. The expanded mast cell population may contribute to the exacerbations of symptoms which occurs when asthmatics are exposed to respiratory infections.

Dataset Information

Lung ?? T Cells Mediate Protective Responses during Neonatal Influenza Infection that Are Associated with Type 2 Immunity.

Publications

Lung γδ T Cells Mediate Protective Responses during Neonatal Influenza Infection that Are Associated with Type 2 Immunity.

Similar Datasets

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