Toll-like receptor-4 (TLR4) mediates human beta-defensin-2 (HBD-2) induction in response to Chlamydia pneumoniae in mononuclear cells.
Monocytes are pivotal effector cells of the innate immune system that are vital for recognizing and eliminating invasive microbial pathogens. When microbial products bind to pathogen-recognition receptors, monocytes are activated and release a broad array of cytokines and defensins that orchestrate the host innate and adaptive immune responses. The aim of the present study is to investigate whether Toll-like receptor-4 (TLR4) mediates human beta-defensin-2 (HBD-2) induction in response to Chlamydia pneumoniae in mononuclear cells. We showed that TLR4 is expressed in U937 cells and monocytes infected with viable microorganisms in a time-dependent fashion, while heat-inactivated microorganisms induced a lesser expression, albeit still significant, of TLR4 compared with viable organisms; flow cytometric analysis, in particular, revealed a higher level of TLR4 expression at 48 and 72 h postinfection. In addition, U937 cells and monocytes responded to C. pneumoniae in a TLR4-dependent manner with induction of mRNA and protein of the antimicrobial peptide HBD-2. The treatment of cells with TLR4-neutralizing antibody resulted in a decrease in C. pneumoniae-induced HBD-2 production. This study reveals that TLRs not only recognize ligands but also the types of effector molecules induced, namely, antimicrobial peptides. An understanding of the importance of the TLR-mediated antimicrobial mechanisms may provide new avenues for the development of therapeutic regimens aimed at activating the body's own defenses by stimulating TLR-dependent pathways.
Romano Carratelli
Caterina
C
Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Faculty of Medicine and Surgery, Second University of Naples, Naples, Italy. caterina.romanocarratelli@unina2.it
Mazzola
Nello
N
Paolillo
Rossella
R
Sorrentino
Sabato
S
Rizzo
Antonietta
A
D002478:Cells, Cultured; D023521:Chlamydophila Infections / Q000276:immunology* / Q000382:microbiology; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D003627:Data Interpretation, Statistical; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology* / Q000378:metabolism; D020298:U937 Cells; D023083:beta-Defensins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
C106641:DEFB4A protein, human; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D023083:beta-Defensins