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Differential roles of MyD88 and TRIF in hematopoietic and resident cells during murine gram-negative pneumonia.
J Infect Dis 2012; 206(9):1415-23JI

Abstract

BACKGROUND

Pneumonia is frequently caused by gram-negative pathogens, among which Klebsiella pneumoniae prominently features. Recognition of pathogen-associated molecular patterns by Toll-like receptors (TLRs) is important for an appropriate immune response during infection. TLR signaling can proceed via 2 distinct routes that are dependent on the adaptor proteins Myeloid differentiation primary response gene (88) (MyD88) and TIR-domain-containing adaptor-inducing interferon-β (TRIF). The aim of the study was to determine the relative contribution of MyD88 and TRIF signaling in resident and hematopoietic cells to host defense during pneumonia.

METHODS

Bone marrow chimeras of MyD88 deficient/wild type and TRIF mutant/wild type mice were created and infected with K. pneumoniae via the airways.

RESULTS

MyD88 in both resident and hematopoietic cells contributed to survival and antibacterial defense in late-stage infection, whereas only TRIF in hematopoietic cells was protective. On the other hand, resident MyD88 and hematopoietic TRIF contributed to distant cellular injury. Resident MyD88 was pivotal for early chemokine release and neutrophil recruitment in the bronchoalveolar space.

CONCLUSIONS

MyD88- and TRIF-dependent signaling has a differential contribution to host defense in different cell types that changes from early- to late-stage gram-negative pneumonia.

Authors+Show Affiliations

Center of Infection and Immunity, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22904341

Citation

van Lieshout, Miriam H P., et al. "Differential Roles of MyD88 and TRIF in Hematopoietic and Resident Cells During Murine Gram-negative Pneumonia." The Journal of Infectious Diseases, vol. 206, no. 9, 2012, pp. 1415-23.
van Lieshout MH, Blok DC, Wieland CW, et al. Differential roles of MyD88 and TRIF in hematopoietic and resident cells during murine gram-negative pneumonia. J Infect Dis. 2012;206(9):1415-23.
van Lieshout, M. H., Blok, D. C., Wieland, C. W., de Vos, A. F., van 't Veer, C., & van der Poll, T. (2012). Differential roles of MyD88 and TRIF in hematopoietic and resident cells during murine gram-negative pneumonia. The Journal of Infectious Diseases, 206(9), pp. 1415-23. doi:10.1093/infdis/jis505.
van Lieshout MH, et al. Differential Roles of MyD88 and TRIF in Hematopoietic and Resident Cells During Murine Gram-negative Pneumonia. J Infect Dis. 2012;206(9):1415-23. PubMed PMID: 22904341.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential roles of MyD88 and TRIF in hematopoietic and resident cells during murine gram-negative pneumonia. AU - van Lieshout,Miriam H P, AU - Blok,Dana C, AU - Wieland,Catharina W, AU - de Vos,Alex F, AU - van 't Veer,Cornelis, AU - van der Poll,Tom, Y1 - 2012/08/16/ PY - 2012/8/21/entrez PY - 2012/8/21/pubmed PY - 2013/1/5/medline SP - 1415 EP - 23 JF - The Journal of infectious diseases JO - J. Infect. Dis. VL - 206 IS - 9 N2 - BACKGROUND: Pneumonia is frequently caused by gram-negative pathogens, among which Klebsiella pneumoniae prominently features. Recognition of pathogen-associated molecular patterns by Toll-like receptors (TLRs) is important for an appropriate immune response during infection. TLR signaling can proceed via 2 distinct routes that are dependent on the adaptor proteins Myeloid differentiation primary response gene (88) (MyD88) and TIR-domain-containing adaptor-inducing interferon-β (TRIF). The aim of the study was to determine the relative contribution of MyD88 and TRIF signaling in resident and hematopoietic cells to host defense during pneumonia. METHODS: Bone marrow chimeras of MyD88 deficient/wild type and TRIF mutant/wild type mice were created and infected with K. pneumoniae via the airways. RESULTS: MyD88 in both resident and hematopoietic cells contributed to survival and antibacterial defense in late-stage infection, whereas only TRIF in hematopoietic cells was protective. On the other hand, resident MyD88 and hematopoietic TRIF contributed to distant cellular injury. Resident MyD88 was pivotal for early chemokine release and neutrophil recruitment in the bronchoalveolar space. CONCLUSIONS: MyD88- and TRIF-dependent signaling has a differential contribution to host defense in different cell types that changes from early- to late-stage gram-negative pneumonia. SN - 1537-6613 UR - https://www.unboundmedicine.com/medline/citation/22904341/Differential_roles_of_MyD88_and_TRIF_in_hematopoietic_and_resident_cells_during_murine_gram_negative_pneumonia_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1093/infdis/jis505 DB - PRIME DP - Unbound Medicine ER -