PMID- 15778382 OWN - NLM STAT- MEDLINE DCOM- 20050607 LR - 20190516 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 174 IP - 7 DP - 2005 Apr 1 TI - Inverse correlation of maturity and antibacterial activity in human dendritic cells. PG - 4203-9 AB - Dendritic cells (DCs) are a key part of host defense against microbial pathogens, being part of the innate immune system, but also instructing the adaptive T cell response. This study was designed to evaluate whether human DCs directly contribute to innate immunity by killing intracellular bacteria, using tuberculosis as a model. DCs were detected in bronchoalveolar lavage samples indicating that DCs are available for immediate interaction with Mycobacterium tuberculosis (M. Tb) after inhalation of the pathogen. The phenotype of DC in bronchoalveolar lavage closely resembles monocyte-derived immature DC (iDC) according to the expression of CD1a, CD83, and CCR7. The antimicrobial activity of iDC against intracellular M. Tb inversely correlated with TNF-alpha-release and was enhanced by treatment with anti-TNF-alpha Abs. Differentiation of iDC into mature DC by addition of TNF-alpha or activation via Toll-like receptors further reduced killing of M. Tb. The antibacterial activity against intracellular M. Tb of all DCs was significantly lower than alveolar macrophages. Therefore, the maintenance of a pool of DCs at the site of disease activity in tuberculosis, and the maturation of these DC by TNF-alpha provides a mechanism by which M. Tb escapes the innate immune system. FAU - Buettner, Maike AU - Buettner M AD - Institut fur Klinische Mikrobiologie, Immunologie und Hygiene, Universitat Erlangen-Nurnberg, Erlangen, Germany. FAU - Meinken, Christoph AU - Meinken C FAU - Bastian, Max AU - Bastian M FAU - Bhat, Rauf AU - Bhat R FAU - Stossel, Elmar AU - Stossel E FAU - Faller, Gerhard AU - Faller G FAU - Cianciolo, George AU - Cianciolo G FAU - Ficker, Joachim AU - Ficker J FAU - Wagner, Manfred AU - Wagner M FAU - Rollinghoff, Martin AU - Rollinghoff M FAU - Stenger, Steffen AU - Stenger S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Bacteria/growth & development/*immunology MH - Bronchoalveolar Lavage MH - *Cell Differentiation MH - Cells, Cultured MH - Dendritic Cells/*cytology/*immunology MH - Humans MH - *Immunity, Innate MH - Immunophenotyping MH - Macrophages, Alveolar/immunology MH - Mycobacterium tuberculosis/growth & development/immunology MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 2005/03/22 09:00 MHDA- 2005/06/09 09:00 CRDT- 2005/03/22 09:00 PHST- 2005/03/22 09:00 [pubmed] PHST- 2005/06/09 09:00 [medline] PHST- 2005/03/22 09:00 [entrez] AID - 174/7/4203 [pii] AID - 10.4049/jimmunol.174.7.4203 [doi] PST - ppublish SO - J Immunol. 2005 Apr 1;174(7):4203-9. doi: 10.4049/jimmunol.174.7.4203.