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

Abstract

Naked mole-rats (NM-R; Heterocephalus glaber ) live in multi-generational colonies with a social hierarchy, and show low cancer incidence and long life-spans. Here we asked if an immune component might underlie such extreme physiology. The largest lymphoid organ is the spleen, which plays an essential role in responding 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 NM-Rs. Spleen size in healthy NM-Rs showed considerable inter-individual variability, with some animals displaying enlarged spleens. In all healthy NM-Rs, the spleen is a major site of adult haematopoiesis under normal physiological conditions. However, myeloid-to-lymphoid cell ratio is increased and splenic marginal zone showed markedly altered morphology when compared to other rodents. Healthy NM-Rs with enlarged spleens showed potentially better anti-microbial profiles and were much more likely to have a high rank within the colony. We propose that the anatomical plasticity of the spleen might be regulated by social interaction and gives immunological advantage to increase the lifespan of higher-ranked animals.

The best of both worlds: no apparent trade-off between immunity and reproduction in two group-living African mole-rat species

“…Monocytes destroy foreign substances by phagocytosis and enhance the efficiency of the other immune cells (table 1). Furthermore, there is evidence that BFs possess a more robust adaptive immunity through higher lymphocyte (likely in the form of memory cells) prevalence, similar to other African mole-rat species [51]. An increased prevalence of adaptive immune system components, particularly memory cells, would indicate an increased ability to protect the body against specific foreign pathogens, such as E. coli , a common pathogen found in soils and on plant roots (mole-rats' main food source).…”

“…An increased prevalence of adaptive immune system components, particularly memory cells, would indicate an increased ability to protect the body against specific foreign pathogens, such as E. coli , a common pathogen found in soils and on plant roots (mole-rats' main food source). Interestingly, the Damaraland mole-rat, particularly BF, immune system displays more similarities to those of the naked mole-rat ( Heterocephalus glaber ) and humans ( Homo sapiens ) rather than to those of other rodents [51,52], including increased prevalence of lymphocytes and monocytes in the peripheral blood. Reduced NLR and raised MLR (within the range of healthy [53]) of BFs compared with NBFs indicate that BFs possess a more balanced immune system compared with NBFs (table 1).…”

Bifidobacterium breve CCFM1078 Alleviates Collagen-Induced Arthritis in Rats via Modulating the Gut Microbiota and Repairing the Intestinal Barrier Damage

“…As a result, the colon may not be the primary location of systemic inflammation, which is congruent with findings from colonic H&E staining. As the largest immunological organ, spleen plays a role in the inflammatory response . Through the compromised intestinal barrier, LPS activates the TLR4-MyD88-dependent pathway in the spleen and the expressions of NF-κB and P38.…”

Macrophages from naked mole-rat possess distinct immunometabolic signatures upon polarization

“…The naked mole-rat is a relatively new animal model to study immune system and immunoregulation that attracted a lot of attention due to extraordinary lifespan and apparent resistance to tumorigenesis. Recent studies including single-cell RNA-sequencing-based analysis uncovered a crucial difference in the immune organ structure and cell composition of NMR as compared to a mouse, the most frequently studied model organism in the immunological research ( 1 – 3 ). NMR possesses an expanded myeloid compartment comprised of granulocytes and macrophages and reduced lymphoid cell populations such as cytotoxic T-lymphocytes (CTL), B and NK cells ( 1 , 3 ), in agreement with the previously reported enhanced susceptibility of these animals to viral infections ( 4 , 5 ).…”

“…Recent studies including single-cell RNA-sequencing-based analysis uncovered a crucial difference in the immune organ structure and cell composition of NMR as compared to a mouse, the most frequently studied model organism in the immunological research ( 1 – 3 ). NMR possesses an expanded myeloid compartment comprised of granulocytes and macrophages and reduced lymphoid cell populations such as cytotoxic T-lymphocytes (CTL), B and NK cells ( 1 , 3 ), in agreement with the previously reported enhanced susceptibility of these animals to viral infections ( 4 , 5 ). This can be partially explained by “myeloid bias” observed in bone marrow hematopoiesis of NMR ( 2 ).…”