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Infection and Immunity, March 2008, p. 935-941, Vol. 76, No. 3
0019-9567/08/$08.00+0     doi:10.1128/IAI.01218-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Expression of Cathelicidin LL-37 during Mycobacterium tuberculosis Infection in Human Alveolar Macrophages, Monocytes, Neutrophils, and Epithelial Cells{triangledown}

Bruno Rivas-Santiago,1 Rogelio Hernandez-Pando,2 Claudia Carranza,3 Esmeralda Juarez,3 Juan Leon Contreras,2 Diana Aguilar-Leon,2 Martha Torres,3 and Eduardo Sada3*

Unidad de Investigación Médica-Zacatecas, IMSS, Zacatecas, México,1 Departamento de Investigación en Microbiología, Instituto Nacional de Enfermedades Respiratorias, Mexico City, México,3 Departamento de Investigación en Patología, Instituto Nacional de Ciencias Médicas y Nutrición SZ, Mexico City, México2

Received 4 September 2007/ Returned for modification 16 October 2007/ Accepted 13 December 2007

The innate immune response in human tuberculosis is not completely understood. To improve our knowledge regarding the role of cathelicidin hCAP-18/LL37 in the innate immune response to tuberculosis infection, we used immunohistochemistry, immunoelectron microscopy, and gene expression to study the induction and production of the antimicrobial peptide in A549 epithelial cells, alveolar macrophages (AM), neutrophils, and monocyte-derived macrophages (MDM) after infection with Mycobacterium tuberculosis. We demonstrated that mycobacterial infection induced the expression and production of LL-37 in all cells studied, with AM being the most efficient. We did not detect peptide expression in tuberculous granulomas, suggesting that LL-37 participates only during early infection. Through the study of Toll-like receptors (TLR) in MDM, we showed that LL-37 can be induced by stimulation through TLR-2, TLR-4, and TLR-9. This last TLR was strongly stimulated by M. tuberculosis DNA. We concluded that LL-37 may have an important role in the innate immune response against M. tuberculosis.

* Corresponding author. Mailing address: Department of Research in Microbiology, National Institute for Respiratory Diseases, Calzada de Tlalpam 4502, Section XVI, Mexico 1408, Mexico. Phone: 52 55 56664539, ext. 117. Fax: 52 55 5487 1739. E-mail: eduardosadadiaz{at}yahoo.com

{triangledown} Published ahead of print on 26 December 2007.

Editor: R. P. Morrison

Infection and Immunity, March 2008, p. 935-941, Vol. 76, No. 3
0019-9567/08/$08.00+0     doi:10.1128/IAI.01218-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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