Animal Models of Mycobacteria Infection

Abstract

This manuscript describes the infection of mice and guinea pigs with mycobacteria via various routes, as well as necropsy methods for the determination of mycobacterial loads within target organs. Additionally, methods for cultivating mycobacteria and preparing stocks are described. The protocols outlined are primarily used for M. tuberculosis, but can also be used for the study of other non‐tuberculosis mycobacterial species. A wide variety of animal models have been used to test new vaccines, drugs, and the impact of cigarette exposure. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Aerosol infection of mice with mycobacteria Basic Protocol 2: Aerosol infection of guinea pig with mycobacteria using a Madison chamber Alternate Protocol 1: Cigarette exposure prior to infection of mice with mycobacteria Alternate Protocol 2: Intravenous infection of mice with mycobacteria Basic Protocol 3: Necropsy methods for animals experimentally infected with mycobacteria Basic Protocol 4: Following the course of infection Basic Protocol 5: Measuring the animal immune response to infection Support Protocol: Cultivation of mycobacteria for use in animal experiments

Non-Tuberculous Mycobacteria Interference with BCG-Current Controversies and Future Directions

“…Immunity against M.tb requires a balance between immune responses that kill or at least constrain mycobacterial replication [3] and immune regulation to dampen tissue-damaging inflammation. One example that strongly supports the importance of a protective cellular response against M. tb [4,5] is individuals with the acquired immunodeficiency syndrome (AIDS), who have increased susceptibility to M. tb due to a deficiency of CD4+ T cells [4,6]. Before the development of the highly-active anti-retroviral cocktail therapies that are currently used against HIV infection, disseminated infections due to the non-tuberculous mycobacteria (NTM), particularly with Mycobacterium avium complex (MAC), were relatively common, further revealing the importance of the CD4+ T cells in host defense against mycobacteria [7,8].…”

One Size Fits All? Not in In Vivo Modeling of Tuberculosis Chemotherapeutics

“…Dunkin-Hartley Guinea pigs (Cavia porcellus; GP) are extremely susceptible to developing tuberculosis with progressive disease and a range of lesion types, making them an attractive model for drug testing and vaccine studies (Clark et al, 2014;Martinez et al, 2019;Chan et al, 2020). These animals have been infected through aerosol generation, IV or IP injections, or instillation via the nares or trachea, although low-dose aerosols may be the most common route in recent experiments ( Table 1).…”

The double‐edged sword of Tregs in M tuberculosis, M avium, and M. abscessus infection

“…Mtb and, to a lesser degree M avium 91,92 is individuals with the acquired immunodeficiency syndrome (AIDS) increased susceptibility to Mtb due to a deficiency of CD4 + T cells. Before the development of the highly active antiretroviral cocktail therapies that are currently…”

“…Immunity against Mycobacteria requires a balance between immune responses that kill or at least constrain Mycobacteria replication and immune regulation to dampen tissue‐damaging inflammation 3 . One example that strongly supports the importance of a protective cellular response against Mtb and, to a lesser degree M avium 91,92 is individuals with the acquired immunodeficiency syndrome (AIDS) increased susceptibility to Mtb due to a deficiency of CD4 + T cells. Before the development of the highly active antiretroviral cocktail therapies that are currently used against HIV infection, disseminated infections due to the NTM, particularly with MAC, were relatively common, further revealing the importance of the CD4 + T cells in host defense against mycobacteria.…”