TY - JOUR
T1 - Function of SLAM-Associated Protein (SAP) in Acute Pneumoseptic Bacterial Infection
AU - Tripathi, Jitendra K.
AU - Sharma, Atul
AU - Gupta, Kuldeep
AU - Abdelrahman, Houda
AU - Chauhan, Pooja
AU - Mishra, Bibhuti B.
AU - Sharma, Jyotika
N1 - Funding Information:
This work was supported by the National Institutes of Health (Grants R21AI107457 and R01AI121804 to J.S.; P20GM113123 to J.S. and B.B.M.). The flow cytometry core facility at UND is supported by INBRE and COBRE (Grants P20GM103442 and P20GM113123 ), and the imaging and histology core facilities are supported by COBRE (Grant P20GM113123 ) from the National Institutes of Health. The authors thank Dr. Steven Clegg, University of Iowa, for providing GFP-labeled K. pneumoniae . We also thank Ms. Sarah Abrahamson and Dr. Bryon Grove for technical assistance with imaging.
Publisher Copyright:
© 2019
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2019/10/4
Y1 - 2019/10/4
N2 - Sepsis resulting from acute pneumonic infections by Gram-negative bacteria is often characterized by dysfunction of innate immune components. Here we report a previously unrecognized innate protective function of SAP, an adaptor protein primarily reported in T cells, NK cells, and NKT cells, during acute pneumonic infection with Klebsiella pneumoniae (KPn). SAP-deficient mice were highly susceptible to this infection with elevated systemic bacterial spread and increased lung damage. While the overall influx of infiltrating cells in the lungs remained largely intact, increased mortality of SAP-deficient mice correlated with increased accumulation of large NK1.1 + cells harboring bacteria and an impairment of neutrophil extracellular trap formation in vivo during KPn pneumonia, which likely facilitated bacterial outgrowth. Neutrophils were found to express SAP; however, adoptive transfer experiment supported a neutrophil-extrinsic function of SAP in neutrophil extracellular trap formation. Collectively, these data present the first report depicting innate protective function of SAP in an acute pulmonary infection.
AB - Sepsis resulting from acute pneumonic infections by Gram-negative bacteria is often characterized by dysfunction of innate immune components. Here we report a previously unrecognized innate protective function of SAP, an adaptor protein primarily reported in T cells, NK cells, and NKT cells, during acute pneumonic infection with Klebsiella pneumoniae (KPn). SAP-deficient mice were highly susceptible to this infection with elevated systemic bacterial spread and increased lung damage. While the overall influx of infiltrating cells in the lungs remained largely intact, increased mortality of SAP-deficient mice correlated with increased accumulation of large NK1.1 + cells harboring bacteria and an impairment of neutrophil extracellular trap formation in vivo during KPn pneumonia, which likely facilitated bacterial outgrowth. Neutrophils were found to express SAP; however, adoptive transfer experiment supported a neutrophil-extrinsic function of SAP in neutrophil extracellular trap formation. Collectively, these data present the first report depicting innate protective function of SAP in an acute pulmonary infection.
KW - neutrophil extracellular traps
KW - neutrophils
KW - NK1.1+ cells
KW - phagocytes
KW - SLAM-associated protein, SAP, Sh2d1a
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U2 - 10.1016/j.jmb.2019.07.002
DO - 10.1016/j.jmb.2019.07.002
M3 - Article
C2 - 31295456
AN - SCOPUS:85070493965
SN - 0022-2836
VL - 431
SP - 4345
EP - 4353
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 21
ER -