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Host response of platelet-activating factor receptor-deficient mice during pulmonary tuberculosis
Sebastiaan Weijer1, Jaklien C Leemans, Sandrine Florquin
1Laboratory of Experimental Internal Medicine, Department of Infectious Diseases, Tropical Medicine and AIDS, Department of Pathology, Academic Medical Centre, University of Amsterdam, The Netherlands. s.weijer@amc.uva.nl
Abstract:
Platelet-activating factor (PAF) is a phospholipid with potent, diverse actions, which has been implicated as an important mediator in host defence against several intracellular pathogens. To determine the role of PAF in host defence in pulmonary tuberculosis, PAF receptor-deficient (PAFR-/-) and wild-type (PAFR+/+) mice were infected intranasally with a virulent strain of Mycobacterium tuberculosis. Mycobacterial outgrowth in lungs and liver did not differ significantly between PAFR-/- and PAFR+/+ mice at 2 or 6 weeks postinfection. After 28 weeks, 86% of PAFR-/- mice and 79% of PAFR+/+ mice had died (non-significant). In addition, both mouse strains were indistinguishable with respect to histopathology, the recruitment and activation of lymphocytes, and cytokine concentrations in the lung. These data suggest that PAF is not involved in the protective immune response to tuberculosis.
Insights
Platelet-activating factor (PAF) does not play a role in the immune response to tuberculosis. Studies using PAF receptor-deficient mice showed no significant difference in controlling Mycobacterium tuberculosis infection compared to wild-type mice.
Area of Science:
- Immunology
- Microbiology
- Pathology
Background:
- Platelet-activating factor (PAF) is a phospholipid mediator with diverse biological actions.
- PAF has been implicated in host defense mechanisms against intracellular pathogens.
Purpose of the Study:
- To investigate the role of Platelet-activating factor (PAF) in host defense during pulmonary tuberculosis.
- To determine if PAF receptor deficiency impacts the course of Mycobacterium tuberculosis infection in mice.
Main Methods:
- Intranasal infection of wild-type (PAFR+/+) and PAF receptor-deficient (PAFR-/-) mice with Mycobacterium tuberculosis.
- Assessment of mycobacterial outgrowth in lungs and liver at 2 and 6 weeks post-infection.
- Evaluation of survival rates, histopathology, lymphocyte responses, and lung cytokine concentrations at 28 weeks.
Main Results:
- No significant difference in mycobacterial outgrowth was observed between PAFR-/- and PAFR+/+ mice at early time points.
- Survival rates at 28 weeks were similar between the two mouse strains (86% vs 79%).
- Histopathology, lymphocyte activation, and cytokine profiles in the lungs were indistinguishable between groups.
Conclusions:
- Platelet-activating factor (PAF) is not essential for the protective immune response against pulmonary tuberculosis.
- The absence of PAF signaling does not alter the susceptibility or disease progression in a murine model of tuberculosis.