The Immunopathologic Effects of Mycoplasma pneumoniae and Community-acquired Respiratory Distress Syndrome Toxin. A Primate Model

Abstract

Mycoplasma pneumoniae infection has been linked to poor asthma outcomes. M. pneumoniae produces an ADP-ribosylating and vacuolating toxin called community-acquired respiratory distress syndrome (CARDS) toxin that has a major role in inflammation and airway dysfunction. The objective was to evaluate the immunopathological effects in primates exposed to M. pneumoniae or CARDS toxin. A total of 13 baboons were exposed to M. pneumoniae or CARDS toxin. At Days 7 and 14, BAL fluid was collected and analyzed for cell count, percent of each type of cell, CARDS toxin by PCR, CARDS toxin by antigen capture, eosinophilic cationic protein, and cytokine profiles. Serum IgM, IgG, and IgE responses to CARDS toxin were measured. All animals had a necropsy for analysis of the histopathological changes on lungs. No animal developed signs of infection. The serological responses to CARDS toxin were variable. At Day 14, four of seven animals exposed to M. pneumoniae and all four animals exposed to CARDS toxin developed histological "asthma-like" changes. T cell intracellular cytokine analysis revealed an increasing ratio of IL-4/IFN-γ over time. Both M. pneumoniae and CARDS toxin exposure resulted in similar histopathological pulmonary changes, suggesting that CARDS toxin plays a major role in the inflammatory response.

Keywords: asthma; community-acquired respiratory distress syndrome toxin; mycoplasma; primate model.

Figure 1.

(A) Mild (<50%) grade of multilayered cellular infiltrates reflected visually in scanned lung section; lesions with fewer cell infiltrates are not evident in the scans. (B) Moderate (50–75%) grade of multilayered cellular infiltrates reflected visually in scanned lung section. (C) Severe (75–100%) grade of multilayered cellular infiltrates reflected visually in scanned lung section. Treated right lower lobe (upper panel) and “untreated control” left lower lobe (lower panel) of the same animal are illustrated in each case. CARDS = community-acquired respiratory distress syndrome; LLL = left lower lobe; MP = Mycoplasma pneumoniae; RLL = right lower lobe.

Figure 2.

(A) IgM antibody response to CARDS toxin and Mycoplasma pneumoniae organisms as determined by ELISA. (B) IgG antibody response to CARDS toxin and M. pneumoniae organisms as determined by ELISA. OD = optical density.

Figure 3.

Proportion of peripheral blood intracellular IFN-γ (A) IL-17, (B) IL-4, and (C) in total T cells in baboons exposed to CARDS toxin (dotted lines) or M. pneumoniae at baseline, Day 7, and Day 14. (D) Shows the intercellular IL-4/IFN-γ ratio of peripheral blood cells at baseline, Day 7, and Day 14.