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2017 ; 7
(1
): 7262
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SH3GLB2/endophilin B2 regulates lung homeostasis and recovery from severe
influenza A virus infection
#MMPMID28779131
Fino KK
; Yang L
; Silveyra P
; Hu S
; Umstead TM
; DiAngelo S
; Halstead ES
; Cooper TK
; Abraham T
; Takahashi Y
; Zhou Z
; Wang HG
; Chroneos ZC
Sci Rep
2017[Aug]; 7
(1
): 7262
PMID28779131
show ga
New influenza A viruses that emerge frequently elicit composite inflammatory
responses to both infection and structural damage of alveolar-capillary barrier
cells that hinders regeneration of respiratory function. The host factors that
relinquish restoration of lung health to enduring lung injury are insufficiently
understood. Here, we investigated the role of endophilin B2 (B2) in
susceptibility to severe influenza infection. WT and B2-deficient mice were
infected with H1N1 PR8 by intranasal administration and course of influenza
pneumonia, inflammatory, and tissue responses were monitored over time.
Disruption of B2 enhanced recovery from severe influenza infection as indicated
by swift body weight recovery and significantly better survival of endophilin
B2-deficient mice compared to WT mice. Compared to WT mice, the B2-deficient
lungs exhibited induction of genes that express surfactant proteins, ABCA3,
GM-CSF, podoplanin, and caveolin mRNA after 7 days, temporal induction of
CCAAT/enhancer binding protein CEBP?, ?, and ? mRNAs 3-14 days after infection,
and differences in alveolar extracellular matrix integrity and respiratory
mechanics. Flow cytometry and gene expression studies demonstrated robust
recovery of alveolar macrophages and recruitment of CD4+ lymphocytes in
B2-deficient lungs. Targeting of endophilin B2 alleviates adverse effects of IAV
infection on respiratory and immune cells enabling restoration of alveolar
homeostasis.
|Adaptor Proteins, Signal Transducing/genetics/*metabolism
[MESH]