<i>Burkholderia pseudomallei</i> stimulates low interleukin-8 production in the human lung epithelial cell line A549

Utaisincharoen, Pongsak; Anuntagool, Narisara; Arjcharoen, S.; Lengwehasatit, I.; Limposuwan, K.; Chaisuriya, P.; Sirisinha, Stitaya

doi:10.1111/j.1365-2249.2004.02601.x

Cited by 18 publications

(19 citation statements)

References 25 publications

(33 reference statements)

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“…In response to stimuli, IkB␣ is degraded by the proteasome, resulting in NF-B nuclear translocation. Previously, we demonstrated that the level of I B␣ degradation in human lung epithelial A549 cells infected with B. pseudomallei is lower than that in cells infected with other Gram-negative bacteria, including Salmonella enterica serovar Typhi (27). A low level of I B␣ degradation was also observed in B. pseudomallei-infected macrophages compared to that observed in LPS mutant (Fig.…”

Section: Discussionmentioning

confidence: 84%

Burkholderia pseudomallei-Induced Expression of a Negative Regulator, Sterile-α and Armadillo Motif-Containing Protein, in Mouse Macrophages: a Possible Mechanism for Suppression of the MyD88-Independent Pathway

2011

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Burkholderia pseudomallei, a causative agent of melioidosis, is a Gram-negative facultative intracellular bacterium that can survive and multiply in macrophages. Previously, we demonstrated that B. pseudomallei failed to activate gene expression downstream of the MyD88-independent pathway, particularly the expression of beta interferon (IFN-␤) and inducible nitric oxide synthase (iNOS), leading to the inability of macrophages to kill this bacterium. In the present report, we extended our study to show that B. pseudomallei was able to activate sterile-␣ and Armadillo motif (SARM)-containing protein, a known negative regulator of the MyD88-independent pathway. Both live B. pseudomallei and heat-killed B. pseudomallei were able to upregulate SARM expression in a time-dependent manner in mouse macrophage cell line RAW 264.7. The expression of SARM required bacterial internalization, as it could be inhibited by cytochalasin D. In addition, the intracellular survival of B. pseudomallei was suppressed in SARM-deficient macrophages. Increased expression of IFN-␤ and iNOS and degradation of I B␣ correlated with enhanced macrophage killing capability. These results demonstrated that B. pseudomallei modulated macrophage defense mechanisms by upregulating SARM, thus leading to the suppression of IFN-␤ and iNOS needed for bacterial elimination.

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Section: Discussionmentioning

confidence: 84%

Burkholderia pseudomallei-Induced Expression of a Negative Regulator, Sterile-α and Armadillo Motif-Containing Protein, in Mouse Macrophages: a Possible Mechanism for Suppression of the MyD88-Independent Pathway

2011

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“…pseudomallei suppresses NF-kB activation B. pseudomallei was shown to be less stimulatory to epithelial cells and macrophages compared with other Gram-negative bacteria (28,29). We have previously reported that B. pseudomallei activates low levels of NF-kB via TLR2, TLR4, and TLR5 (31).…”

Section: Resultsmentioning

confidence: 99%

Suppression of Host Innate Immune Response by Burkholderia pseudomallei through the Virulence Factor TssM

Tan

Chen²,

Lim

et al. 2010

The Journal of Immunology

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Burkholderia pseudomallei is a Gram-negative saprophyte that is the causative agent of melioidosis, a severe infectious disease endemic in Northern Australia and Southeast Asia. This organism has sparked much scientific interest in the West because of its classification as a potential bioterrorism agent by the U.S. Centers for Disease Control and Prevention. However, relatively little is known about its pathogenesis. We demonstrate that B. pseudomallei actively inhibits NF-κB and type I IFN pathway activation, thereby downregulating host inflammatory responses. We found the virulence factor TssM to be responsible for this activity. TssM interferes with the ubiquitination of critical signaling intermediates, including TNFR-associated factor-3, TNFR-associated factor-6, and IκBα. The expression but not secretion of TssM is regulated by the type III secretion system. We demonstrate that TssM is important for B. pseudomallei infection in vivo as inflammation in the tssM mutant-infected mice is more severe and corresponds to a more rapid death compared with wild-type bacteria-infected mice. Abs to TssM can be detected in the sera of melioidosis patients, indicating that TssM is functionally expressed in vivo and thus could contribute to bacterial pathogenesis in human melioidosis.

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“…TLR4 expression on memory T cells has been reported (4) and, although stimulation via LPS alone does not result in proliferation nor cytokine production, T cells are able to respond to LPS via TLR4 by upregulating adherence to fibronectin and SOCS3 (39). Thus, LPS may be able to directly costimulate human T cells during B. pseudomallei infection, although LPS from B. pseudomallei has been described as less stimulatory (34). This non-antigen-specific stimulation could serve to perpetuate and maintain longterm T-cell memory.…”

Section: Vol 76 2008 B Pseudomallei Infection Costimulates T Cellsmentioning

confidence: 99%

Burkholderia pseudomallei Infection of T Cells Leads to T-Cell Costimulation Partially Provided by Flagellin

Lee

Sun

et al. 2008

Infect Immun

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Burkholderia pseudomallei is the causative agent of melioidosis. While adaptive immunity has been shown to be important for host resistance to B. pseudomallei, the direct interaction of the bacteria with adaptive immune cells such as T and B cells is not well known. To address this question, we infected Jurkat T cells, as well as human primary CD4؉ and CD8 ؉ T cells, with live B. pseudomallei. We found that live bacterial infection could costimulate T cells to produce interleukin-2 (IL-2) and gamma interferon (IFN-␥) in the presence of anti-CD3 cross-linking antibodies. Bacterial supernatant could also costimulate T cells, and this was due to the presence of flagellin in the supernatant. However, T cells infected with bacterial mutants lacking flagellin showed strong impairment in IL-2 but only a slight impairment in IFN-␥ production. When cross-linking of CD3 is replaced by IL-2, live bacterial infection was still able to costimulate human primary T cells to produce IFN-␥ and flagellin is only a minor ligand contributing to this costimulation. Thus, live B. pseudomallei could potentially costimulate T cells not only in an antigen-specific manner but also in a nonspecific manner through bystander activation via IL-2.Burkholderia pseudomallei is a gram-negative bacterium responsible for causing melioidosis, an infectious disease endemic in Southeast Asia and Northern Australia. The bacterium can invade and replicate in both cultured phagocytic (18, 28) and nonphagocytic cells (19). The type III secretion system 3 (TTSS3), also known as the Burkholderia secretion apparatus, enables B. pseudomallei to escape from the endosome into the cytoplasm of infected cells (29). Furthermore, the BimA protein found on one pole of the bacteria helps to facilitate intracellular spread by the formation of actin comet tails (30). These characteristics of the bacterium could help it to survive intracellularly. Upon phagocytosis by macrophages, B. pseudomallei is able to activate the suppressor of cytokine signaling 3 (SOCS3) and cytokine-inducible Src homology 2-containing protein, resulting in a decrease in the gamma interferon (IFN-␥) signaling response (9). We had previously shown that B. pseudomallei infection of monocytes, macrophages, and dendritic cells induced caspase-1-dependent cell death (32). The interference with host innate immune cells such as macrophages could have a profound impact on the innate immune response to bacteria, as well as on the development of the adaptive immune response.The interaction of B. pseudomallei with other immune cells, particularly those from the adaptive immune response such as T and B cells, is not well known. It has been shown that patients surviving melioidosis developed a cell-mediated immune response (20) and, in mice, B. pseudomallei-specific CD4 T cells are important for host resistance in adaptive immunity (16). This means that the ability of the host to develop a robust T-cell response is likely critical in controlling the infection, and there is a possibility that bacteria could ...

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Burkholderia pseudomallei stimulates low interleukin-8 production in the human lung epithelial cell line A549

Cited by 18 publications

References 25 publications

Burkholderia pseudomallei-Induced Expression of a Negative Regulator, Sterile-α and Armadillo Motif-Containing Protein, in Mouse Macrophages: a Possible Mechanism for Suppression of the MyD88-Independent Pathway

Burkholderia pseudomallei-Induced Expression of a Negative Regulator, Sterile-α and Armadillo Motif-Containing Protein, in Mouse Macrophages: a Possible Mechanism for Suppression of the MyD88-Independent Pathway

Suppression of Host Innate Immune Response by Burkholderia pseudomallei through the Virulence Factor TssM

Burkholderia pseudomallei Infection of T Cells Leads to T-Cell Costimulation Partially Provided by Flagellin

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