Dysregulation of TNF-α and IFN-γ expression is a common host immune response in a chronically infected mouse model of melioidosis when comparing multiple human strains of Burkholderia pseudomallei.

Autor: Amemiya K; Bacteriology Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA. kei.amemiya.vol@mail.mil., Dankmeyer JL; Bacteriology Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA., Bearss JJ; Pathology Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA., Zeng X; Pathology Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA., Stonier SW; Virology Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA., Soffler C; Bacteriology Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA., Cote CK; Bacteriology Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA., Welkos SL; Bacteriology Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA., Fetterer DP; Bacteriology Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA., Chance TB; Pathology Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA., Trevino SR; Bacteriology Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA., Worsham PL; Bacteriology Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA., Waag DM; Bacteriology Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA.
Jazyk: angličtina
Zdroj: BMC immunology [BMC Immunol] 2020 Feb 03; Vol. 21 (1), pp. 5. Date of Electronic Publication: 2020 Feb 03.
DOI: 10.1186/s12865-020-0333-9
Abstrakt: Background: Melioidosis is endemic in Southeast Asia and Northern Australia and is caused by the Gram-negative, facultative intracellular pathogen Burkholderia pseudomallei. Diagnosis of melioidosis is often difficult because of the protean clinical presentation of the disease, and it may mimic other diseases, such as tuberculosis. There are many different strains of B. pseudomallei that have been isolated from patients with melioidosis, but it was not clear if they could cause a similar disease in a chronic BALB/c murine model of melioidosis. Hence, we wanted to examine chronically infected mice exposed to different strains of B. pseudomallei to determine if there were differences in the host immune response to the pathogen.
Results: We identified common host immune responses exhibited in chronically infected BALB/c mice, although there was some heterogeneity in the host response in chronically infected mice after exposure to different strains of B. pseudomallei. They all displayed pyogranulomatous lesions in their spleens with a large influx of monocytes/macrophages, NK cells, and neutrophils identified by flow cytometry. Sera from chronically infected mice by ELISA exhibited elevated IgG titers to the pathogen, and we detected by Luminex micro-bead array technology a significant increase in the expression of inflammatory cytokines/chemokines, such as IFN-γ, IL-1α, IL-1β, KC, and MIG. By immunohistochemical and in situ RNA hybridization analysis we found that the increased expression of proinflammatory cytokines (IL-1α, IL-1β, TNF-α, IFN-γ) was confined primarily to the area with the pathogen within pyogranulomatous lesions. We also found that cultured splenocytes from chronically infected mice could express IFN-γ, TNF-α, and MIP-1α ex vivo without the need for additional exogenous stimulation. In addition by flow cytometry, we detected significant amounts of intracellular expression of TNF-α and IFN-γ without a protein transport blocker in monocytes/macrophages, NK cells, and neutrophils but not in CD4 + or CD8 + T cells in splenocytes from chronically infected mice.
Conclusion: Taken together the common features we have identified in chronically infected mice when 10 different human clinical strains of B. pseudomallei were examined could serve as biomarkers when evaluating potential therapeutic agents in mice for the treatment of chronic melioidosis in humans.
Databáze: MEDLINE
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