The Unusual Immune System of the Naked Mole-Rat

The immune system plays a critical role in host defense to pathogens, tissue homeostasis, cancer development, and several aging-associated chronic inflammatory diseases. The naked mole-rat (Heterocephalus glaber) is a subterranean rodent with both extraordinary longevity and cancer-resistant phenotypes. Unlike the immune system of standard laboratory rodents, that of the naked mole-rat features a higher myeloid-to-lymphoid ratio, lacks natural killer cells, has higher pro-inflammatory cytokine production in macrophages, and exhibits a novel LPS-responsive neutrophil subset that highly expresses several antimicrobials. Given these unusual features, the potential involvement of the naked mole-rat's immune system in their longevity and cancer-resistance remains enigmatic. In this chapter, we summarize the current knowledge of the immune system in the naked mole-rat, including the immune cell repertoire, the primary and secondary lymphoid organs, and the inflammatory responses to the pathogenic stimulation such as bacterial toxins. We compare these findings to published studies of the other subterranean rodents and discuss how the environmental factors in which they have evolved may have influenced their immune function.