Inflammation in Lung infections are Regulated by Released Pathogen-toxin CARDS BioNews Texas

A new study entitled “ADP-Ribosylation of NLRP3 by Mycoplasma pneumoniae CARDS Toxin Regulates Inflammasome Activity” describes a new mechanism used by Mycoplasma pneumoniae via its toxin CARDS to activate host inflammasome, a key regulator of inflammation. The study was published in the journal mBio.

Mycoplasma pneumonia is a human pathogen responsible for causing both acute and chronic lung infections, and exacerbating the symptoms related to asthma and wheezing. It is also the cause of a condition known as community-acquired pneumonia (lung infections developed outside of a hospital), a mild-case of pneumonia. In this study, the authors discovered a unique mechanism of action of pathogen toxin CARDS (short for Community Acquired Respiratory Distress Syndrome), a key bacterial toxin inducer of lung infections. Specifically, the authors showed CARDS toxin activates NLRP3, a key component of the inflammasome complex, a crucial regulator of host inflammatory response.

While this response is important to fight infections, an excessive release of proinflamatory cytokines leads to a state of “hyperactivation” and causes damaging to the host tissues. This is particular important in the setting of chronic diseases such as those of the lungs – asthma and COPD. CARDS catalyzes the ADP-ribosylation of NLRP3, which the authors found to lead to inflamasome activation. The team highlights that their findings foster new studies to understand further the link between CARDs and inflammasome activation, which will result in new therapeutic avenues for patients suffering from both acute and chronic lung infections.

[adrotate group=”15″]Joel B. Baseman, Ph.D., professor of microbiology and immunology in the School of Medicine at the UT Health Science Center in San Antonio and director of the Center for Airway Inflammation Research (cAIR) and study leading author commented, “Inflammation is important for self-protection from infection and any injury, but when a microbial factor such as the CARDS toxin controls inflammation, bad things happen. Through this mechanism, CARDS toxin triggers exaggerated and prolonged inflammation that results in tissue injury, airway narrowing, mucus hypersecretion, wheezing and coughing.”

Thirumalai R. Kannan, Ph.D., associate professor/research in the Department of Microbiology and Immunology at the UT Health Science Center added, “Now that we have identified this pathway of disease development, our goal is to prevent the wide range of airway pathologies caused by CARDS toxin with drugs, vaccines and protective antibodies. We are undertaking those studies now.”