Dipeptidyl peptidase I-dependent neutrophil recruitment modulates the inflammatory response to Sendai virus infection.
The role of innate immunity in the pathogenesis of asthma is unclear. Although increased presence of neutrophils is associated with persistent asthma and asthma exacerbations, how neutrophils participate in the pathogenesis of asthma remains controversial. In this study, we show that the absence of dipeptidyl peptidase I (DPPI), a lysosomal cysteine protease found in neutrophils, dampens the acute inflammatory response and the subsequent mucous cell metaplasia that accompanies the asthma phenotype induced by Sendai virus infection. This attenuated phenotype is accompanied by a significant decrease in the accumulation of neutrophils and the local production of CXCL2, TNF, IL-1beta, and IL-6 in the lung of infected DPPI-/- mice. Adoptive transfer of DPPI-sufficient neutrophils into DPPI-/- mice restored the levels of CXCL2 and enhanced cytokine production on day 4 postinfection and subsequent mucous cell metaplasia on day 21 postinfection. These results indicate that DPPI and neutrophils play a critical role in Sendai virus-induced asthma phenotype as a result of a DPPI-dependent neutrophil recruitment and cytokine response.
Akk
Antonina M
AM
Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Simmons
Pamela M
PM
Chan
Happy W
HW
Agapov
Eugene
E
Holtzman
Michael J
MJ
Grayson
Mitchell H
MH
Pham
Christine T N
CT
D000818:Animals; D001249:Asthma / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D020789:Cathepsin C / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007249:Inflammation / Q000201:enzymology / Q000276:immunology / Q000821:virology; D008297:Male; D008679:Metaplasia / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology* / Q000473:pathology*; D020545:Respiratory Mucosa / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D010253:Respirovirus Infections / Q000201:enzymology / Q000276:immunology* / Q000473:pathology*; D029082:Sendai virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000276:immunology / Q000473:pathology
D020789:Cathepsin C