Mast cells inhibit intramacrophage Francisella tularensis replication via contact and secreted products including IL-4

Jyothi M. Ketavarapu, Annette R. Rodriguez, Jieh Juen Yu, Yu Cong, Ashlesh K. Murthy, Thomas G. Forsthuber, M. Neal Guentzel, Karl E. Klose, Michael T. Berton, Bernard P. Arulanandam

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Francisella tularensis is an intracellular, Gram-negative bacterium that is the causative agent of pulmonary tularemia. The pathogenesis and mechanisms related to innate resistance against F. tularensis are not completely understood. Mast cells are strategically positioned within mucosal tissues, the major interface with the external environment, to initiate innate responses at the site of infection. Mast cell numbers in the cervical lymph nodes and the lungs progressively increased as early as 48 h after intranasal F. tularensis live vaccine strain (LVS) challenge. We established a primary bone marrow-derived mast cell-macrophage coculture system and found that mast cells significantly inhibit F. tularensis LVS uptake and growth within macrophages. Importantly, mice deficient in either mast cells or IL-4 receptor displayed greater susceptibility to the infection when compared with corresponding wild-type animals. Contact-dependent events and secreted products including IL-4 from mast cells, and IL-4 production from other cellular sources, appear to mediate the observed protective effects. These results demonstrate a previously unrecognized role for mast cells and IL-4 and provide a new dimension to our understanding of the innate immune mechanisms involved in controlling intramacrophage Francisella replication.

Original languageEnglish (US)
Pages (from-to)9313-9318
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number27
DOIs
StatePublished - Jul 8 2008

Keywords

  • Innate
  • LVS
  • Macrophages
  • Mucosal
  • Pulmonary

ASJC Scopus subject areas

  • General

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