LL-37 immunomodulatory activity during Mycobacterium tuberculosis infection in macrophages.
Tuberculosis is one of the most important infectious diseases worldwide. The susceptibility to this disease depends to a great extent on the innate immune response against mycobacteria. Host defense peptides (HDP) are one of the first barriers to counteract infection. Cathelicidin (LL-37) is an HDP that has many immunomodulatory effects besides its weak antimicrobial activity. Despite advances in the study of the innate immune response in tuberculosis, the immunological role of LL-37 during M. tuberculosis infection has not been clarified. Monocyte-derived macrophages were infected with M. tuberculosis strain H37Rv and then treated with 1, 5, or 15 μg/ml of exogenous LL-37 for 4, 8, and 24 h. Exogenous LL-37 decreased tumor necrosis factor alpha (TNF-α) and interleukin-17 (IL-17) while inducing anti-inflammatory IL-10 and transforming growth factor β (TGF-β) production. Interestingly, the decreased production of anti-inflammatory cytokines did not reduce antimycobacterial activity. These results are consistent with the concept that LL-37 can modulate the expression of cytokines during mycobacterial infection and this activity was independent of the P2X7 receptor. Thus, LL-37 modulates the response of macrophages during infection, controlling the expression of proinflammatory and anti-inflammatory cytokines.
Medical Research Unit-Zacatecas, Mexican Institute for Social Security-IMSS, Zacatecas, Mexico.
Flor
F
Torres-Juarez
Medical Research Unit-Zacatecas, Mexican Institute for Social Security-IMSS, Zacatecas, Mexico.
Albertina
A
Cardenas-Vargas
Medical Research Unit-Zacatecas, Mexican Institute for Social Security-IMSS, Zacatecas, Mexico.
Alejandra
A
Montoya-Rosales
Medical Research Unit-Zacatecas, Mexican Institute for Social Security-IMSS, Zacatecas, Mexico.
Irma
I
González-Curiel
Medical Research Unit-Zacatecas, Mexican Institute for Social Security-IMSS, Zacatecas, Mexico.
Mariana H
MH
Garcia-Hernandez
Medical Research Unit-Zacatecas, Mexican Institute for Social Security-IMSS, Zacatecas, Mexico.
Jose A
JA
Enciso-Moreno
Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC, Canada.
Robert E W
RE
Hancock
Medical Research Unit-Zacatecas, Mexican Institute for Social Security-IMSS, Zacatecas, Mexico rondo_vm@yahoo.com.
Bruno
B
Rivas-Santiago
D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D002460:Cell Line; D004306:Dose-Response Relationship, Immunologic; D015870:Gene Expression; D006801:Humans; D007113:Immunity, Innate; D007155:Immunologic Factors / Q000494:pharmacology*; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects; D061251:Primary Cell Culture; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; C508609:IL10 protein, human; D007155:Immunologic Factors; D020381:Interleukin-17; D058486:Receptors, Purinergic P2X7; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D054804:Cathelicidins