TY - JOUR
T1 - Defensin production by human limbo-corneal fibroblasts infected with mycobacteria
AU - Castañeda-Sánchez, Jorge I.
AU - García-Pérez, Blanca E.
AU - Muñoz-Duarte, Ana R.
AU - Baltierra-Uribe, Shantal L.
AU - Mejia-López, Herlinda
AU - López-López, Carlos
AU - Bautista-De Lucio, Victor M.
AU - Robles-Contreras, Atzín
AU - Luna-Herrera, Julieta
PY - 2013/2/4
Y1 - 2013/2/4
N2 - 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.
AB - 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.
KW - Cathelicidin LL-37
KW - Fibroblast cytoskeleton
KW - Fibroblasts
KW - Human beta-defensin
KW - IL-6
KW - Limbo-corneal cells
KW - Mycobacterium abscessus
KW - Mycobacterium smegmatis
KW - Mycobacterium tuberculosis
UR - http://www.scopus.com/inward/record.url?scp=84947436964&partnerID=8YFLogxK
U2 - 10.3390/pathogens2010013
DO - 10.3390/pathogens2010013
M3 - Artículo
SN - 2076-0817
VL - 2
SP - 13
EP - 32
JO - Pathogens
JF - Pathogens
IS - 1
ER -