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Defensin Production by Human Limbo-Corneal Fibroblasts Infected with Mycobacteria
Department of Immunology, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala S/N, 11340 México, D.F., Mexico
Research Unit, Instituto de Oftalmología Conde de Valenciana, Chimalpopoca 14 Colonia Obrera, 06800 México DF, Mexico
Biomedical Research Center, Hospital Nuestra Señora de la Luz, IAP. Ezequiel Montes 135, 06030 México DF, Mexico
* Author to whom correspondence should be addressed.
Received: 9 December 2012; in revised form: 24 December 2012 / Accepted: 24 January 2013 / Published: 4 February 2013
Abstract: Epithelial cells of the cornea and the conjunctiva constitutively produce antimicrobial peptides; however, the production of defensins by other cell types located around the eye has not been investigated. We analyzed the production of beta-defensins (hBD) and cathelicidin LL-37 during the infection of primary limbo-corneal fibroblasts with M. tuberculosis (MTB), M. abscessus (MAB), and M. smegmatis (MSM). The intracellular survival of each mycobacterium, the production of cytokines and the changes on the distribution of the actin filaments during the infection were also analyzed. Fibroblasts produce basal levels of hBD1 and LL-37 and under PMA stimulation they produce hBD2, hBD3 and overexpress hBD1 and LL-37. MAB induced the highest levels of hBD1 and LL-37 and intermediate levels of IL-6; however, MAB was not eliminated. In addition, MAB induced the greatest change to the distribution of the actin filaments. MTB also produced changes in the structure of the cytoskeleton and induced low levels of hBD1 and IL-6, and intermediate levels of LL-37. The balance of these molecules induced by MTB appeared to contribute to the non-replicative state observed in the limbo-corneal cells. MSM induced the lowest levels of hBD1 and LL-37 but the highest levels of IL-6; MSM was eliminated. The results suggest that mycobacterial infections regulate the production of antimicrobial peptides and cytokines, which in conjunction can contribute to the control of the bacilli.
Keywords: human beta-defensin; cathelicidin LL-37; fibroblasts; limbo-corneal cells; Mycobacterium abscessus; Mycobacterium tuberculosis; Mycobacterium smegmatis; fibroblast cytoskeleton; IL-6
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Castañeda-Sánchez, J.I.; García-Pérez, B.E.; Muñoz-Duarte, A.R.; Baltierra-Uribe, S.L.; Mejia-López, H.; López-López, C.; Bautista-De Lucio, V.M.; Robles-Contreras, A.; Luna-Herrera, J. Defensin Production by Human Limbo-Corneal Fibroblasts Infected with Mycobacteria. Pathogens 2013, 2, 13-32.
Castañeda-Sánchez JI, García-Pérez BE, Muñoz-Duarte AR, Baltierra-Uribe SL, Mejia-López H, López-López C, Bautista-De Lucio VM, Robles-Contreras A, Luna-Herrera J. Defensin Production by Human Limbo-Corneal Fibroblasts Infected with Mycobacteria. Pathogens. 2013; 2(1):13-32.
Castañeda-Sánchez, Jorge I.; García-Pérez, Blanca E.; Muñoz-Duarte, Ana R.; Baltierra-Uribe, Shantal L.; Mejia-López, Herlinda; López-López, Carlos; Bautista-De Lucio, Victor M.; Robles-Contreras, Atzín; Luna-Herrera, Julieta. 2013. "Defensin Production by Human Limbo-Corneal Fibroblasts Infected with Mycobacteria." Pathogens 2, no. 1: 13-32.