Mycoplasma pneumoniae CARDS toxin induces pulmonary eosinophilic and lymphocytic inflammation

Jorge L. Medina, Jacqueline J. Coalson, Edward G. Brooks, Vicki T. Winter, Adriana Chaparro, Molly F.R. Principe, Thirumalai R. Kannan, Joel B. Baseman, Peter H. Dube

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Mycoplasma pneumoniae causes acute and chronic lung infections in humans, leading to a variety of pulmonary and extrapulmonary sequelae. Of the airway complications of M. pneumoniae infection, M. pneumoniae-associated exacerbation of asthma and pediatric wheezing are emerging as significant sources of human morbidity. However, M. pneumoniae products capable of promoting allergic inflammation are unknown. Recently,wereported that M. pneumoniae produces an ADP-ribosylating and vacuolating toxin termed the community-acquired respiratory distress syndrome (CARDS) toxin. Here we report that naive mice exposed to a single dose of recombinant CARDS (rCARDS) toxin respond with a robust inflammatory response consistent with allergic disease. rCARDS toxin induced 30-fold increased expression of the Th-2 cytokines IL-4 and IL-13 and 70- to 80-fold increased expression of the Th-2 chemokines CCL17 and CCL22, corresponding to a mixed cellular inflammatory response comprised of a robust eosinophilia, accumulation of T cells and B cells, and mucus metaplasia. The inflammatory responses correlate temporally with toxin-dependent increases in airway hyperreactivity characterized by increases in airway restriction and decreases in lung compliance. Furthermore, CARDS toxin-mediated changes in lung function and histopathology are dependent on CD41 T cells. Altogether, the data suggest that rCARDS toxin is capable of inducing allergic-type inflammation in naive animals and may represent a causal factor in M. pneumoniae-associated asthma.

Original languageEnglish (US)
Pages (from-to)815-822
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume46
Issue number6
DOIs
StatePublished - Jun 2012

Keywords

  • Asthma
  • Eosinophilia
  • Mycoplasma pneumoniae
  • T cell
  • rCARDS toxin

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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