Analysis of pulmonary inflammation and function in the mouse and baboon after exposure to Mycoplasma pneumoniae CARDS toxin.
Mycoplasma pneumoniae produces an ADP-ribosylating and vacuolating toxin known as the CARDS (Community Acquired Respiratory Distress Syndrome) toxin that has been shown to be cytotoxic to mammalian cells in tissue and organ culture. In this study we tested the ability of recombinant CARDS (rCARDS) toxin to elicit changes within the pulmonary compartment in both mice and baboons. Animals responded to a respiratory exposure to rCARDS toxin in a dose and activity-dependent manner by increasing the expression of the pro-inflammatory cytokines IL-1alpha, 1beta, 6, 12, 17, TNF-alpha and IFN-gamma. There was also a dose-dependent increase in several growth factors and chemokines following toxin exposure including KC, IL-8, RANTES, and G-CSF. Increased expression of IFN-gamma was observed only in the baboon; otherwise, mice and baboons responded to CARDS toxin in a very similar manner. Introduction of rCARDS toxin to the airways of mice or baboons resulted in a cellular inflammatory response characterized by a dose-dependent early vacuolization and cytotoxicity of the bronchiolar epithelium followed by a robust peribronchial and perivascular lymphocytic infiltration. In mice, rCARDS toxin caused airway hyper-reactivity two days after toxin exposure as well as prolonged airway obstruction. The changes in airway function, cytokine expression, and cellular inflammation correlate temporally and are consistent with what has been reported for M. pneumoniae infection. Altogether, these data suggest that the CARDS toxin interacts extensively with the pulmonary compartment and that the CARDS toxin is sufficient to cause prolonged inflammatory responses and airway dysfunction.
Hardy
R Doug
RD
Department of Internal Medicine and Pediatric Infectious Diseases, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas, United States of America.
Coalson
Jacqueline J
JJ
Peters
Jay
J
Chaparro
Adriana
A
Techasaensiri
Chonnamet
C
Cantwell
Angelene M
AM
Kannan
T R
TR
Baseman
Joel B
JB
Dube
Peter H
PH
D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008168:Lung / Q000378:metabolism* / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009177:Mycoplasma pneumoniae / Q000378:metabolism*; D010215:Papio
D001426:Bacterial Proteins; D001427:Bacterial Toxins; C546120:CARDS toxin, Mycoplasma pneumoniae; D018925:Chemokines; D016207:Cytokines