Assays for Assessing Mycobacterium avium Immunity and Evaluating the Effects of Therapeutics.
| Title: | Assays for Assessing Mycobacterium avium Immunity and Evaluating the Effects of Therapeutics. |
|---|---|
| Authors: | Abate G; Division of Infectious Diseases, Allergy and Immunology, Department of Internal Medicine, School of Medicine, Saint Louis University, St. Louis, MO 63104, USA.; Meza KA; Division of Infectious Diseases, Allergy and Immunology, Department of Internal Medicine, School of Medicine, Saint Louis University, St. Louis, MO 63104, USA.; Colbert CG; Division of Infectious Diseases, Allergy and Immunology, Department of Internal Medicine, School of Medicine, Saint Louis University, St. Louis, MO 63104, USA.; Eickhoff CS; Division of Infectious Diseases, Allergy and Immunology, Department of Internal Medicine, School of Medicine, Saint Louis University, St. Louis, MO 63104, USA. |
| Source: | Pathogens (Basel, Switzerland) [Pathogens] 2024 Oct 15; Vol. 13 (10). Date of Electronic Publication: 2024 Oct 15. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101596317 Publication Model: Electronic Cited Medium: Print ISSN: 2076-0817 (Print) Linking ISSN: 20760817 NLM ISO Abbreviation: Pathogens Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI AG, 2012- |
| MeSH Terms: | Mycobacterium avium-intracellulare Infection*/immunology ; Mycobacterium avium-intracellulare Infection*/drug therapy ; Interferon-gamma*/immunology ; Interferon-gamma*/metabolism ; Mycobacterium avium Complex*/immunology; T-Lymphocytes/immunology ; Flow Cytometry/methods ; BCG Vaccine/immunology ; Clarithromycin/therapeutic use ; Clarithromycin/pharmacology ; Animals ; Mice ; Humans ; Disease Models, Animal ; Enzyme-Linked Immunospot Assay ; Female ; Mice, Inbred C57BL |
| Abstract: | In Europe and North America, the prevalence of pulmonary nontuberculous mycobacteria (NTM) is increasing. Most pulmonary NTM infections are caused by the Mycobacterium avium complex (MAC). Sadly, the treatment of pulmonary MAC is suboptimal with failure rates ranging from 37% to 58%. Therefore, there is a need to develop new therapeutics. Developing new immunotherapies and studying their interaction with standard or new drugs requires reliable assays. Four different assays including CFSE-based flow cytometry, in vitro protection assays, IFN-γ ELISPOT, and murine infection models were optimized using a reference strain of MAC (ATCC 700898) to help with the development of immunotherapies for MAC. Expansion of proliferating and IFN-γ producing human T cells is optimal after 7 days of stimulation with MAC at a multiplicity of infection (MOI) of 0.1, achieving a stimulation index of 26.5 ± 11.6 (mean ± SE). The in vitro protection assay for MAC works best by co-culturing T cells expanded for 7 days with MAC (MOI 1)-infected autologous macrophages. Aerosol MAC infection of mice allows measurement of the effects of the BCG vaccine and clarithromycin. IFN-γ ELISPOT assays with live MAC (MOI 3) stimulation of splenocytes from mice immunized with BCG help identify differences between unimmunized mice and mice immunized with BCG. In conclusion, multiple assays are available for use to identify MAC-specific effector T cells, which will help in the development of new therapeutics or vaccines against pulmonary MAC. |
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| Contributed Indexing: | Keywords: MAC; NTM; T cells; immunotherapy; macrophages; murine |
| Substance Nomenclature: | 82115-62-6 (Interferon-gamma); 0 (BCG Vaccine); H1250JIK0A (Clarithromycin) |
| Entry Date(s): | Date Created: 20241025 Date Completed: 20250303 Latest Revision: 20250313 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11510112 |
| DOI: | 10.3390/pathogens13100903 |
| PMID: | 39452774 |
| Database: | MEDLINE |
Journal Article