Mast Cells Protect Mice from Mycoplasma Pneumonia

Xu, Xin; Zhang, Dongji; Lyubynska, Natalya; Wolters, Paul J.; Killeen, Nigel; Bałuk, Peter; McDonald, Donald M.; Hawgood, Samuel; Caughey, George H.

doi:10.1164/rccm.200507-1034oc

Cited by 77 publications

(86 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[1][2][3][4][5][7][8][9][10][11]13 We therefore decided to examine the role of mast cells and mast cell-derived TNF in another model of severe bacterial infection. S. typhimurium is a Gram-negative intracellular pathogen that causes a deadly systemic infection in mice that resembles typhoid fever in humans.…”

Section: Mast Cell-derived Tnf Can Contribute To Bacterial Proliferatmentioning

confidence: 99%

“…Studies conducted using genetically mast cell-deficient (WB/ReJ ϫ C57BL/6)F 1 [1][2][3][4][5][6][7][8][9][10][11][12][13] defined herein as infections that result in relatively low mortality in normal mice. Although mast cells can contribute to host defense against bacteria by multiple direct and indirect mechanisms, [1][2][3][4][5][7][8][9][10][11][12][13] several groups have focused on the potential role of mast cell-derived tumor necrosis factor (TNF) in such settings. [1][2][3][4][5]7 Results obtained in work using TNFdeficient mice 4 or mice in which the actions of TNF are blocked by neutralizing antibodies 1,2 have clearly demonstrated that TNF can have protective functions during some bacterial infections, and that such TNF-dependent effects may include the enhancement of neutrophil recruitment and/or function and the promotion of bacterial clearance.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Mast Cell-Derived TNF Can Exacerbate Mortality during Severe Bacterial Infections in C57BL/6-Kit Mice

Piliponsky

Chen

Grimbaldeston

et al. 2010

The American Journal of Pathology

129

174

View full text Add to dashboard Cite

We used mast cell-engrafted genetically mast cell-deficient C57BL/6-Kit W-sh/W-sh mice to investigate the roles of mast cells and mast cell-derived tumor necrosis factor in two models of severe bacterial infection. In these mice, we confirmed findings derived from studies of mast cell-deficient WBB6F 1 -Kit W/W-v mice indicating that mast cells can promote survival in cecal ligation and puncture (CLP) of moderate severity. However, we found that the beneficial role of mast cells in this setting can occur independently of mast cell-derived tumor necrosis factor. By contrast, using mast cell-engrafted C57BL/6-Kit W-sh/W-sh mice, we found that mast cell-derived tumor necrosis factor can increase mortality during severe CLP and can also enhance bacterial growth and hasten death after intraperitoneal inoculation of Salmonella typhimurium. In WBB6F 1 -Kit W-sh/W-sh mice, mast cells enhanced survival during moderately severe CLP but did not significantly change the survival observed in severe CLP. Our findings in three types of genetically mast celldeficient mice thus support the hypothesis that, depending on the circumstances (including mouse strain background, the nature of the mutation resulting in a mast cell deficiency, and type and severity of infection), mast cells can have either no detectable effect or opposite effects on survival during bacterial infections, eg, promoting survival during moderately severe CLP associated with low mortality but, in C57BL/ 6-Kit W-sh/W-sh mice, increasing mortality during severe CLP or infection with S. typhimurium. (Am J Pathol

show abstract

Section: Mast Cell-derived Tnf Can Contribute To Bacterial Proliferatmentioning

confidence: 99%

mentioning

confidence: 99%

Mast Cell-Derived TNF Can Exacerbate Mortality during Severe Bacterial Infections in C57BL/6-Kit Mice

Piliponsky

Chen

Grimbaldeston

et al. 2010

The American Journal of Pathology

129

174

View full text Add to dashboard Cite

show abstract

“…Importantly, mast cells are strategically positioned in the lungs to initiate innate responses at this site of infection (23) and to selectively migrate into regional lymph nodes to influence the development of adaptive immunity (18). Specifically, mast cells have been demonstrated to be important in mediating protective immunity against Gram-negative and Mycoplasma-induced pneumonias (24)(25)(26)(27). The extensive phenotypic plasticity of mast cells, their proximity to primary sites of infection, and their potential to influence important aspects of the immune response, all likely contribute to their function in the immune response to bacterial infection.…”

mentioning

confidence: 99%

Mast cells inhibit intramacrophageFrancisella tularensisreplication via contact and secreted products including IL-4

Ketavarapu

Rodriguez

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

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.innate ͉ LVS ͉ macrophages ͉ mucosal ͉ pulmonary

show abstract

“…ADA (1 U/ml), an enzyme that breaks down adenosine to inosine, significantly decreased basal tPA activity (73.3 6 3.7% of control response; n = 9; p , 0.0001); it abolished adenosine-dependent tPA activity and reduced it below basal level (72.0 6 3.5% of control response; n = 9; p , 0.0001) ( Fig. 2A) 3 ], 1 mM each) (n = 18, p , 0.0001). This mixture also reduced the control response slightly, but significantly (6%; p = 0.0247).…”

Section: Adenosine Potentiates Mast Cell Line Hmc-1 Tpa Activitymentioning

confidence: 91%

Adenosine Potentiates Human Lung Mast Cell Tissue Plasminogen Activator Activity

Sereda

Bradding

Vial

2011

The Journal of Immunology

View full text Add to dashboard Cite

We investigated whether adenosine, a potent contributor to the regulation of pulmonary function, can modulate human lung mast cell (HLMC) fibrinolytic activity. Tissue plasminogen activator (tPA) activity and tPA transcript expression levels from a human mast cell line (HMC-1) and HLMC were monitored following adenosine application. Adenosine potentiated mast cell tPA activity and tPA gene expression in a dose-dependent manner. Adenosine effects were abolished in the presence of adenosine deaminase. HMC-1 cells and HLMC predominantly expressed adenosine A2A and A2B receptor transcripts (A2B ≈ A2A > A3 >> A1). Pharmacological and signaling studies suggest that the A2A receptor is the major subtype accounting for adenosine-induced mast cell tPA activity. Finally, the supernatant from HMC-1 cells and HLMC treated with adenosine (for 24 h) significantly increased fibrin clot lysis, whereas ZM241385, an A2A receptor antagonist, abolished this effect. To our knowledge, this study provides the first data to demonstrate the potentiating effect of adenosine on mast cell tPA activity and fibrin clot lysis.

show abstract

Mast Cells Protect Mice from Mycoplasma Pneumonia

Cited by 77 publications

References 42 publications

Mast Cell-Derived TNF Can Exacerbate Mortality during Severe Bacterial Infections in C57BL/6-Kit Mice

Mast Cell-Derived TNF Can Exacerbate Mortality during Severe Bacterial Infections in C57BL/6-Kit Mice

Mast cells inhibit intramacrophageFrancisella tularensisreplication via contact and secreted products including IL-4

Adenosine Potentiates Human Lung Mast Cell Tissue Plasminogen Activator Activity

Contact Info

Product

Resources

About