Intradermal Inoculation of <em>Mycobacterium avium</em> in the Mouse Ear

In contrast to natural nontuberculous mycobacterial (NTM) exposures or infections whose pathology is founded on a slow-replicating organism, the aerosol infection in a mouse model can cause an elevated proliferation of bacterial growth in the lungs. Chronic aerosol and systemic infections can be treated with anti-mycobacterial drugs, which could also reflect a prior exposure, but these procedures are lengthy and less representative of natural exposures. The goal of this protocol is to develop a less invasive mouse model of NTM exposure-like conditions that are more translational. Here, we describe a method to intradermally challenge preclinical mice through ear tissue using Mycobacterium avium (M. avium) to mimic an exposure and enable immune responses to the bacteria without obvious disease. In this article, we describe the intradermal ear injection method and confirm the presence of sustained and contained mycobacterial infection, which provides further opportunities to interrogate the immune responses in this in vivo model.