Mast cell TLR2 signaling is crucial for effective killing of Francisella tularensis

Annette R. Rodriguez, Jieh Juen Yu, M. Neal Guentzel, Christopher S. Navara, Karl E. Klose, Thomas G. Forsthuber, James P. Chambers, Michael T. Berton, Bernard P. Arulanandam

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

TLR signaling is critical for early host defense against pathogens, but the contributions of mast cell TLR-mediated mechanisms and subsequent effector functions during pulmonary infection are largely unknown. We have previously demonstrated that mast cells, through the production of IL-4, effectively control Francisella tularensis replication. In this study, the highly human virulent strain of F. tularensis SCHU S4 and the live vaccine strain were used to investigate the contribution of mast cell/TLR regulation of Francisella. Mast cells required TLR2 for effective bacterial killing, regulation of the hydrolytic enzyme cathepsin L, and for coordination and trafficking of MHC class II and lysosomal-associated membrane protein 2. Infected TLR2 -/- mast cells, in contrast to wild-type and TLR4 -/- cells, lacked detectable IL-4 and displayed increased cell death with a 2-3 log increase of F. tularensis replication, but could be rescued with rIL-4 treatment. Importantly, MHC class II and lysosomal-associated membrane protein 2 localization with labeled F. tularensis in the lungs was greater in wild-type than in TLR2 -/- mice. These results provide evidence for the important effector contribution of mast cells and TLR2-mediated signaling on early innate processes in the lung following pulmonary F. tularensis infection and provide additional insight into possible mechanisms by which intracellular pathogens modulate respiratory immune defenses.

Original languageEnglish (US)
Pages (from-to)5604-5611
Number of pages8
JournalJournal of Immunology
Volume188
Issue number11
DOIs
StatePublished - Jun 1 2012

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Rodriguez, A. R., Yu, J. J., Guentzel, M. N., Navara, C. S., Klose, K. E., Forsthuber, T. G., Chambers, J. P., Berton, M. T., & Arulanandam, B. P. (2012). Mast cell TLR2 signaling is crucial for effective killing of Francisella tularensis. Journal of Immunology, 188(11), 5604-5611. https://doi.org/10.4049/jimmunol.1200039