PMID- 26627460 OWN - NLM STAT- MEDLINE DCOM- 20171023 LR - 20230203 IS - 1935-3456 (Electronic) IS - 1933-0219 (Print) IS - 1933-0219 (Linking) VI - 9 IP - 5 DP - 2016 Sep TI - Lung epithelium and myeloid cells cooperate to clear acute pneumococcal infection. PG - 1288-302 LID - 10.1038/mi.2015.128 [doi] AB - The Gram-positive bacterium Streptococcus pneumoniae causes life-threatening infections, especially among immunocompromised patients. The host's immune system senses S. pneumoniae via different families of pattern recognition receptors, in particular the Toll-like receptor (TLR) family that promotes immune cell activation. Yet, while single TLRs are dispensable for initiating inflammatory responses against S. pneumoniae, the central TLR adapter protein myeloid differentiation factor 88 (MyD88) is of vital importance, as MyD88-deficient mice succumb rapidly to infection. Since MyD88 is ubiquitously expressed in hematopoietic and non-hematopoietic cells, the extent to which MyD88 signaling is required in different cell types to control S. pneumoniae is unknown. Therefore, we used novel conditional knockin mice to investigate the necessity of MyD88 signaling in distinct lung-resident myeloid and epithelial cells for the initiation of a protective immune response against S. pneumoniae. Here, we show that MyD88 signaling in lysozyme M (LysM)- and CD11c-expressing myeloid cells, as well as in pulmonary epithelial cells, is critical to restore inflammatory cytokine and antimicrobial peptide production, leading to efficient neutrophil recruitment and enhanced bacterial clearance. Overall, we show a novel synergistic requirement of compartment-specific MyD88 signaling in S. pneumoniae immunity. FAU - Dudek, M AU - Dudek M AD - Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany. FAU - Puttur, F AU - Puttur F AD - Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany. FAU - Arnold-Schrauf, C AU - Arnold-Schrauf C AD - Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany. FAU - Kuhl, A A AU - Kuhl AA AD - Department of Medicine I for Gastroenterology, Infectious Disease and Rheumatology, Campus Benjamin Franklin, Charite-Universitatsmedizin, Berlin, Germany. FAU - Holzmann, B AU - Holzmann B AD - Department of Surgery, Technische Universitat Munchen, Munich, Germany. FAU - Henriques-Normark, B AU - Henriques-Normark B AD - Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. AD - Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden. FAU - Berod, L AU - Berod L AD - Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany. FAU - Sparwasser, T AU - Sparwasser T AD - Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151202 PL - United States TA - Mucosal Immunol JT - Mucosal immunology JID - 101299742 RN - 0 (CD11c Antigen) RN - 0 (Myd88 protein, mouse) RN - 0 (Myeloid Differentiation Factor 88) RN - EC 3.2.1.17 (Muramidase) RN - EC 3.2.1.17 (lysozyme M, mouse) SB - IM MH - Animals MH - CD11c Antigen/genetics/immunology MH - Cell Communication/immunology MH - Epithelial Cells/*immunology/microbiology MH - Gene Expression Regulation MH - Gene Knock-In Techniques MH - Lung/*immunology/microbiology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Muramidase/genetics/immunology MH - Myeloid Differentiation Factor 88/genetics/*immunology MH - Neutrophil Infiltration MH - Neutrophils/*immunology/microbiology MH - Pneumonia, Pneumococcal/genetics/*immunology/microbiology MH - Signal Transduction MH - Streptococcus pneumoniae/growth & development/immunology/pathogenicity PMC - PMC4990776 EDAT- 2015/12/03 06:00 MHDA- 2017/10/24 06:00 PMCR- 2016/08/19 CRDT- 2015/12/03 06:00 PHST- 2015/07/01 00:00 [received] PHST- 2015/11/01 00:00 [accepted] PHST- 2015/12/03 06:00 [entrez] PHST- 2015/12/03 06:00 [pubmed] PHST- 2017/10/24 06:00 [medline] PHST- 2016/08/19 00:00 [pmc-release] AID - S1933-0219(22)00773-5 [pii] AID - 10.1038/mi.2015.128 [doi] PST - ppublish SO - Mucosal Immunol. 2016 Sep;9(5):1288-302. doi: 10.1038/mi.2015.128. Epub 2015 Dec 2.