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2017 ; 8
(2
): ä Nephropedia Template TP
gab.com Text
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English Wikipedia
Contribution of the Purinergic Receptor P2X7 to Development of Lung
Immunopathology during Influenza Virus Infection
#MMPMID28351919
Leyva-Grado VH
; Ermler ME
; Schotsaert M
; Gonzalez MG
; Gillespie V
; Lim JK
; García-Sastre A
mBio
2017[Mar]; 8
(2
): ä PMID28351919
show ga
An exacerbated immune response is one of the main causes of influenza-induced
lung damage during infection. The molecular mechanisms regulating the fate of the
initial immune response to infection, either as a protective response or as
detrimental immunopathology, are not well understood. The purinergic receptor
P2X7 is an ionotropic nucleotide-gated ion channel receptor expressed on immune
cells that has been implicated in induction and maintenance of excessive
inflammation. Here, we analyze the role of this receptor in a mouse model of
influenza virus infection using a receptor knockout (KO) mouse strain. Our
results demonstrate that the absence of the P2X7 receptor results in a better
outcome to influenza virus infection characterized by reduced weight loss and
increased survival upon experimental influenza challenge compared to wild-type
mice. This effect was not virus strain specific. Overall lung pathology and
apoptosis were reduced in virus-infected KO mice. Production of proinflammatory
cytokines and chemokines such as interleukin-10 (IL-10), gamma interferon
(IFN-?), and CC chemokine ligand 2 (CCL2) was also reduced in the lungs of the
infected KO mice. Infiltration of neutrophils and depletion of CD11b(+)
macrophages, characteristic of severe influenza virus infection in mice, were
lower in the KO animals. Together, these results demonstrate that activation of
the P2X7 receptor is involved in the exacerbated immune response observed during
influenza virus infection.IMPORTANCE A hallmark of influenza virus infection is
the development of lung pathology induced by an exacerbated immune response. The
mechanisms shared by the antiviral host defense required for viral clearance and
those required for development of immunopathology are not clearly understood.
Purinergic receptors, and in particular the purinergic receptor P2X7 (P2X7r), are
involved in activation of the immune response. We used mice lacking the P2X7r
(P2X7r KO mice) to better understand the mechanisms that lead to development of
lung pathology during influenza virus infection. In our studies, we observed that
P2X7r KO mice developed less lung immunopathology and had better survival than
the wild-type mice. These results implicate P2X7r in the induction of an
exacerbated local immune response to influenza virus and help us to better
understand the mechanisms leading to the lung immunopathology observed during
severe viral infections.