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Regulation and Role of Chitotriosidase during Lung Infection with Klebsiella pneumoniae.
Sharma, Lokesh; Amick, Alyssa K; Vasudevan, Swathy; Lee, Sei Won; Marion, Chad R; Liu, Wei; Brady, Virginia; Losier, Ashley; Bermejo, Santos D; Britto, Clemente J; Lee, Chun Geun; Elias, Jack A; Dela Cruz, Charles S.
Afiliação
  • Sharma L; Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT 06520.
  • Amick AK; Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT 06520.
  • Vasudevan S; Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT 06520.
  • Lee SW; Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT 06520.
  • Marion CR; Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT 06520.
  • Liu W; Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT 06520.
  • Brady V; Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT 06520.
  • Losier A; Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT 06520.
  • Bermejo SD; Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT 06520.
  • Britto CJ; Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT 06520.
  • Lee CG; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912; and.
  • Elias JA; Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912; and.
  • Dela Cruz CS; Section of Pulmonary and Critical Care and Sleep Medicine, Department of Medicine, Yale University School of Medicine, New Haven, CT 06520; Charles.delacruz@yale.edu.
J Immunol ; 201(2): 615-626, 2018 07 15.
Article em En | MEDLINE | ID: mdl-29891554
Chitinases and chitinase-like proteins are an evolutionary conserved group of proteins. In the absence of chitin synthesis in mammals, the conserved presence of chitinases suggests their roles in physiology and immunity, but experimental evidence to prove these roles is scarce. Chitotriosidase (chit1) is one of the two true chitinases present in mammals and the most prevalent chitinase in humans. In this study, we investigated the regulation and the role of chit1 in a mouse model of Klebsiella pneumoniae lung infection. We show that chitinase activity in bronchoalveolar lavage fluid is significantly reduced during K. pneumoniae lung infection. This reduced activity is inversely correlated with the number of neutrophils. Further, instilling neutrophil lysates in lungs decreased chitinase activity. We observed degradation of chit1 by neutrophil proteases. In a mouse model, chit1 deficiency provided a significant advantage to the host during K. pneumoniae lung infection by limiting bacterial dissemination. This phenotype was independent of inflammatory changes in chit1-/- mice as they exerted a similar inflammatory response. The decreased dissemination resulted in improved survival in chit1-/- mice infected with K. pneumoniae in the presence or absence of antibiotic therapy. The beneficial effects of chit1 deficiency were associated with altered Akt activation in the lungs. Chit1-/- mice induced a more robust Akt activation postinfection. The role of the Akt pathway in K. pneumoniae lung infection was confirmed by using an Akt inhibitor, which impaired health and survival. These data suggest a detrimental role of chit1 in K. pneumoniae lung infections.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por Klebsiella / Hexosaminidases / Klebsiella pneumoniae / Pulmão / Macrófagos / Neutrófilos Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por Klebsiella / Hexosaminidases / Klebsiella pneumoniae / Pulmão / Macrófagos / Neutrófilos Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article