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Toll-like receptor signaling in airborne Burkholderia thailandensis infection.
Infect Immun. 2009 Dec; 77(12):5612-22.II

Abstract

Melioidosis is a tropical disease endemic in southeast Asia and northern Australia caused by the gram-negative soil saprophyte Burkholderia pseudomallei. Although infection is often systemic, the lung is frequently involved. B. thailandensis is a closely related organism that at high doses causes lethal pneumonia in mice. We examined the role of Toll-like receptors (TLRs), essential components of innate immunity, in vitro and in vivo during murine B. thailandensis pneumonia. TLR2, TLR4, and TLR5 mediate NF-kappaB activation by B. thailandensis in transfected HEK293 or CHO cells. In macrophages, TLR4 and the adaptor molecule MyD88, but not TLR2 or TLR5, are required for tumor necrosis factor alpha production induced by B. thailandensis. In low-dose airborne infection, TLR4 is needed for early, but not late, bacterial containment, and MyD88 is essential for control of infection and host survival. TLR2 and TLR5 are not necessary to contain low-dose infection. In high-dose airborne infection, TLR2 deficiency confers a slight survival advantage. Lung and systemic inflammatory responses are induced by low-dose inhaled B. thailandensis independently of individual TLRs or MyD88. These findings suggest that redundancy in TLR signaling or other MyD88-dependent pathways may be important in pneumonic B. thailandensis infection but that MyD88-independent mechanisms of inflammation are also activated. TLR signaling in B. thailandensis infection is substantially comparable to signaling induced by virulent B. pseudomallei. These studies provide additional insights into the host-pathogen interaction in pneumonic Burkholderia infection.

Authors+Show Affiliations

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98104, USA. tewest@u.washington.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19797072

Citation

West, T Eoin, et al. "Toll-like Receptor Signaling in Airborne Burkholderia Thailandensis Infection." Infection and Immunity, vol. 77, no. 12, 2009, pp. 5612-22.
West TE, Hawn TR, Skerrett SJ. Toll-like receptor signaling in airborne Burkholderia thailandensis infection. Infect Immun. 2009;77(12):5612-22.
West, T. E., Hawn, T. R., & Skerrett, S. J. (2009). Toll-like receptor signaling in airborne Burkholderia thailandensis infection. Infection and Immunity, 77(12), 5612-22. https://doi.org/10.1128/IAI.00618-09
West TE, Hawn TR, Skerrett SJ. Toll-like Receptor Signaling in Airborne Burkholderia Thailandensis Infection. Infect Immun. 2009;77(12):5612-22. PubMed PMID: 19797072.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Toll-like receptor signaling in airborne Burkholderia thailandensis infection. AU - West,T Eoin, AU - Hawn,Thomas R, AU - Skerrett,Shawn J, Y1 - 2009/09/21/ PY - 2009/10/3/entrez PY - 2009/10/3/pubmed PY - 2009/12/16/medline SP - 5612 EP - 22 JF - Infection and immunity JO - Infect Immun VL - 77 IS - 12 N2 - Melioidosis is a tropical disease endemic in southeast Asia and northern Australia caused by the gram-negative soil saprophyte Burkholderia pseudomallei. Although infection is often systemic, the lung is frequently involved. B. thailandensis is a closely related organism that at high doses causes lethal pneumonia in mice. We examined the role of Toll-like receptors (TLRs), essential components of innate immunity, in vitro and in vivo during murine B. thailandensis pneumonia. TLR2, TLR4, and TLR5 mediate NF-kappaB activation by B. thailandensis in transfected HEK293 or CHO cells. In macrophages, TLR4 and the adaptor molecule MyD88, but not TLR2 or TLR5, are required for tumor necrosis factor alpha production induced by B. thailandensis. In low-dose airborne infection, TLR4 is needed for early, but not late, bacterial containment, and MyD88 is essential for control of infection and host survival. TLR2 and TLR5 are not necessary to contain low-dose infection. In high-dose airborne infection, TLR2 deficiency confers a slight survival advantage. Lung and systemic inflammatory responses are induced by low-dose inhaled B. thailandensis independently of individual TLRs or MyD88. These findings suggest that redundancy in TLR signaling or other MyD88-dependent pathways may be important in pneumonic B. thailandensis infection but that MyD88-independent mechanisms of inflammation are also activated. TLR signaling in B. thailandensis infection is substantially comparable to signaling induced by virulent B. pseudomallei. These studies provide additional insights into the host-pathogen interaction in pneumonic Burkholderia infection. SN - 1098-5522 UR - https://www.unboundmedicine.com/medline/citation/19797072/Toll_like_receptor_signaling_in_airborne_Burkholderia_thailandensis_infection_ L2 - https://journals.asm.org/doi/10.1128/IAI.00618-09?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -