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Immune competence and spleen size scale with colony status in the naked mole-rat

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Title:Immune competence and spleen size scale with colony status in the naked mole-rat
Creators Name:Bégay, V. and Cirovic, B. and Barker, A.J. and Klopfleisch, R. and Hart, D.W. and Bennett, N.C. and Lewin, G.R.
Abstract:Naked mole-rats (NM-R; Heterocephalus glaber) live in multi-generational colonies with a social hierarchy, show low cancer incidence and long life-spans. Here we asked if such extreme physiology might have an immune component. The spleen is the largest lymphoid organ and plays an essential role in response to immunological insults and may participate in combating cancer and slowing ageing. We investigated the anatomy, molecular composition and function of the NM-R spleen using RNA-sequencing and histological analysis in healthy animals. We found that spleen size in healthy NM-Rs varies considerably. We therefore classified NM-Rs according to spleen size as NM-Rs with small spleens or enlarged spleens. Animals with enlarged spleens showed potentially better anti-microbial profiles and were much more likely to have a high rank within the colony. Splenomegaly was associated with infection in sick NM-Rs, but not in NM-Rs with enlarged spleens. In all healthy NM-Rs splenic erythropoiesis, megakaryopoiesis and myelopoiesis were increased, but B lymphopoiesis was reduced and splenic marginal zone showed markedly altered morphology when compared to other rodents. However, in NM-Rs lymphocytes were found in secondary sites such as lymph nodes, gut lymphoid nodules and thymus. Thus, the NM-R spleen is a major site of adult hematopoiesis under normal physiological conditions. Overall, the NM-R immune system seems to rely mainly on innate immune responses with a more restricted adaptive immune response. We propose that the anatomical plasticity of the spleen might be regulated by social interaction and gives immunological advantage to increase the life-span of higher ranked animals.
Keywords:Hyperplasic Spleen/Splenomegaly, Adaptive Immune System, Lymphopoiesis, Extramedullary Hematopoiesis, Eusociality, Animals, Mice, Mole-Rats
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2021.08.15.456351
Date:15 August 2021
Official Publication:https://doi.org/10.1101/2021.08.15.456351

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