title: Mycoplasma pneumoniae CARDS toxin induces pulmonary eosinophilic and lymphocytic inflammation.
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, we reported 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 CD4(+) 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.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Medina
authors.forename: Jacqueline J
authors.initials: JJ
authors.lastname: Coalson
authors.forename: Edward G
authors.initials: EG
authors.lastname: Brooks
authors.forename: Vicki T
authors.initials: VT
authors.lastname: Winter
authors.forename: Adriana
authors.initials: A
authors.lastname: Chaparro
authors.forename: Molly F R
authors.initials: MF
authors.lastname: Principe
authors.forename: Thirumalai R
authors.initials: TR
authors.lastname: Kannan
authors.forename: Joel B
authors.initials: JB
authors.lastname: Baseman
authors.forename: Peter H
authors.initials: PH
authors.lastname: Dube
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000166:cytology*; D005434:Flow Cytometry; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D008214:Lymphocytes / Q000166:cytology*; D051379:Mice; D009177:Mycoplasma pneumoniae / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D001427:Bacterial Toxins