title: Toll-like receptor-4 (TLR4) mediates human beta-defensin-2 (HBD-2) induction in response to Chlamydia pneumoniae in mononuclear cells.
abstract: 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.
authors.affiliation: 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
authors.forename: Caterina
authors.initials: C
authors.lastname: Romano Carratelli
authors.forename: Nello
authors.initials: N
authors.lastname: Mazzola
authors.forename: Rossella
authors.initials: R
authors.lastname: Paolillo
authors.forename: Sabato
authors.initials: S
authors.lastname: Sorrentino
authors.forename: Antonietta
authors.initials: A
authors.lastname: Rizzo
mesh_terms: 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
chemical_list: C106641:DEFB4A protein, human; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D023083:beta-Defensins