SESSION TYPE: Cytokines/Cellular Interactions Posters
PRESENTED ON: Wednesday, October 24, 2012 at 01:30 PM - 02:30 PM
PURPOSE: Mp produces an ADP-ribosylating and vacuolating toxin called Community Acquired Respiratory Distress Syndrome toxin (CARDS Tx) that may play a significant role in persistent pulmonary inflammation. We evaluated the immunologic response and histopathological changes in the lungs of primates exposed to Mp or CARDS Tx.
METHODS: Thirteen baboons (Papio sp) underwent bronchoscopic instillation of CARDS Tx (5mg/10 ml; n=4) or Mp (10 8 ccu/10ml; n=9). Serum and BAL were obtained prior to sacrifice on Day 7 (n=6) and 14 (N=7). Immunological response (IgG and IgM), cytology, flow cytometry, and complete necropsy were performed on each animal. A standardized histological injury panel was used to determine severity.
RESULTS: No animal demonstrated clinical or bronchoscopic evidence of infection. 7/13 (54%) of the baboons developed “asthma-like” lesions (mixed eosinophilic and lymphocytic infiltration, mucus metaplasia, and focal mucous plugs) on histological examination, and of these, 3/7 (43%) developed immunological response (IgG and IgM) against Mp or CARDS toxin. 2/4 (50%) had received CARDS Tx and 1/8 (12.5%) Mp instillation. These baboons expressed a positive immunological response only on day 14; all showing histological “asthma-like” lesions and worse inflammation severity scores at necropsy (27.0 +/- 12.1 vs. 9.6 +/- 2.7, p=0.001) compared to the rest of the animals. This subgroup also had a trend towards more eosinophils in bronchial wash (62.1 +/- 22.7% vs. 30.7 +/- 36.3%, p = NS) and a higher IL-4/INF-gamma ratio post exposure (1.47 +/- 1.3 vs. 0.70 +/- 0.62, p= NS) suggesting a TH2 response.
CONCLUSIONS: The immunological response against Mp or CARDS toxin observed was heterogeneous. Despite subclinical infection, an “asthma-like” lesion was identified in over half the animals and the cytokine and cellular response suggested a TH2 response. A positive immunological response correlated with a worse inflammatory response.
CLINICAL IMPLICATIONS: Immunological response to Mp and CARDS toxin may be responsible for persistent pulmonary inflammation and may elicit a TH2 response. Further studies are needed to evaluate the impact of CARDS toxin in chronic inflammatory pulmonary diseases.
DISCLOSURE: The following authors have nothing to disclose: Diego Maselli, Jay Peters, Jorge Medina, Oriol Sibila, Jacqueline Coalson, Edward Brooks, Joel Baseman, Peter Dube
No Product/Research Disclosure InformationDivision of Pulmonary Diseases & Critical Care, University of Texas Health Science Center at San Antonio, San Antonio, TX