Toll-Like Receptor 2 Controls the Gamma Interferon Response to<i>Francisella tularensis</i>by Mouse Liver Lymphocytes

Hong, Kee-Jong; Wickstrum, Jason R.; Parmely, Michael J.

doi:10.1128/iai.00561-07

Cited by 31 publications

(37 citation statements)

References 39 publications

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“…It is possible that F. tularensis also uses multiple receptors for entry into lung epithelial cells and that interruption of various signaling pathways could decrease uptake via various receptors. Toll-like receptors (TLRs) may play a role in the modulation of the immune response to F. tularensis (9,23,54), and functional TLRs are present on ATII cells (2). However, TLRs have not been implicated among macrophage receptors for F. tularensis internalization identified to date (3,38,47 (31).…”

Section: Discussionmentioning

confidence: 99%

Francisella tularensisInvasion of Lung Epithelial Cells

et al. 2008

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Francisella tularensis, a gram-negative facultative intracellular bacterial pathogen, causes disseminating infections in humans and other mammalian hosts. Macrophages and other monocytes have long been considered the primary site of F. tularensis replication in infected animals. However, recently it was reported that F. tularensis also invades and replicates within alveolar epithelial cells following inhalation in a mouse model of tularemia. TC-1 cells, a mouse lung epithelial cell line, were used to study the process of F. tularensis invasion and intracellular trafficking within nonphagocytic cells. Live and paraformaldehyde-fixed F. tularensis live vaccine strain organisms associated with, and were internalized by, TC-1 cells at similar frequencies and with indistinguishable differences in kinetics. Inhibitors of microfilament and microtubule activity resulted in significantly decreased F. tularensis invasion, as did inhibitors of phosphatidylinositol 3-kinase and tyrosine kinase activity. Collectively, these results suggest that F. tularensis epithelial cell invasion is mediated by a preformed ligand on the bacterial surface and driven entirely by host cell processes. Once internalized, F. tularensis-containing endosomes associated with early endosome antigen 1 (EEA1) followed by lysosomeassociated membrane protein 1 (LAMP-1), with peak coassociation frequencies occurring at 30 and 120 min postinoculation, respectively. By 2 h postinoculation, 70.0% (؎ 5.5%) of intracellular bacteria were accessible to antibody delivered to the cytoplasm, indicating vacuolar breakdown and escape into the cytoplasm.

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Section: Discussionmentioning

confidence: 99%

Francisella tularensisInvasion of Lung Epithelial Cells

et al. 2008

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“…The composition of the cellular immune response in the livers of infected mice has provided a potential clue to immune suppression. The histopathology of hepatic tularemia is characterized by the formation of granuloma-like lesions (13)(14)(15), and the role of gamma interferon (IFN-␥) in their development has been demonstrated (6,36,71). We previously characterized the cellular composition of infected livers using specific cell surface markers showing several types of cells that express the myeloid cell marker CD11b (also known as Mac-1) (55).…”

Section: Although the Monocytic Cd11bmentioning

confidence: 99%

Phenotypic, Morphological, and Functional Heterogeneity of Splenic Immature Myeloid Cells in the Host Response to Tularemia

et al. 2012

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ABSTRACTRecent studies have linked accumulation of the Gr-1+CD11b+cell phenotype with functional immunosuppression in diverse pathological conditions, including bacterial and parasitic infections and cancer. Gr-1+CD11b+cells were the largest population of cells present in the spleens of mice infected with sublethal doses of theFrancisella tularensislive vaccine strain (LVS). In contrast, the number of T cells present in the spleens of these mice did not increase during early infection. There was a significant delay in the kinetics of accumulation of Gr-1+CD11b+cells in the spleens of B-cell-deficient mice, indicating that B cells play a role in recruitment and maintenance of this population in the spleens of mice infected withF. tularensis. The splenic Gr-1+CD11b+cells in tularemia were a heterogeneous population that could be further subdivided into monocytic (mononuclear) and granulocytic (polymorphonuclear) cells using the Ly6C and Ly6G markers and differentiated into antigen-presenting cells followingex vivoculture. Monocytic, CD11b+Ly6ChiLy6G−cells but not granulocytic, CD11b+Ly6CintLy6G+cells purified from the spleens of mice infected withF. tularensissuppressed polyclonal T-cell proliferation via a nitric oxide-dependent pathway. Although the monocytic, CD11b+Ly6ChiLy6G−cells were able to suppress the proliferation of T cells, the large presence of Gr-1+CD11b+cells in mice that survivedF. tularensisinfection also suggests a potential role for these cells in the protective host response to tularemia.

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“…Additionally, phagosomal escape of F. tularensis triggers the activation of the AIM2 inflammasome through the recognition of cytosolic bacterial double-stranded DNA (dsDNA) (6)(7)(8)(9). AIM2 inflammasome activation in turn results in the processing and secretion of the proinflammatory cytokines interleukin-1␤ (IL-1␤) and IL-18 as well as the induction of a pyroptotic death pathway in the infected macrophage (6)(7)(8)(9).…”

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confidence: 99%

“…tularensis is recognized by pattern recognition receptors (PRRs), including Toll-like receptor 2 (TLR2) and the PYHIN family member absent in melanoma 2 (AIM2), both of which are critical for defense against infection (5)(6)(7)(8)(9). Sensing of F. tularensis by TLR2 at the macrophage surface leads to the elaboration of a number of proinflammatory cytokines (7). Following phagocytosis by the macrophage, F. tularensis escapes the phagosome into the cytosol of the cell, where it replicates (10,11).…”

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confidence: 99%