| Summary: | The multimammate mouse (<i>Mastomys natalensis; M. natalensis</i>) has been identified as a major reservoir for multiple human pathogens including Lassa virus (LASV), <i>Leishmania</i> spp., <i>Yersinia</i> spp., and <i>Borrelia</i> spp. Although <i>M. natalensis</i> are related to well-characterized mouse and rat species commonly used in laboratory models, there is an absence of established assays and reagents to study the host immune responses of <i>M. natalensis</i>. As a result, there are major limitations to our understanding of immunopathology and mechanisms of immunological pathogen control in this increasingly important rodent species. In the current study, a large panel of commercially available rodent reagents were screened to identify their cross-reactivity with <i>M. natalensis.</i> Using these reagents, ex vivo assays were established and optimized to evaluate lymphocyte proliferation and cytokine production by <i>M. natalensis</i> lymphocytes. In contrast to C57BL/6J mice, lymphocytes from <i>M. natalensis</i> were relatively non-responsive to common stimuli such as phytohaemagglutinin P and lipopolysaccharide. However, they readily responded to concanavalin A stimulation as indicated by proliferation and cytokine production. In summary, we describe lymphoproliferative and cytokine assays demonstrating that the cellular immune responses in <i>M. natalensis</i> to commonly used mitogens differ from a laboratory-bred mouse strain.
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