Phenotypic and functional characterization of the major lymphocyte populations in the fruit-eating bat Pteropus alecto

Abstract

The unique ability of bats to act as reservoir for viruses that are highly pathogenic to humans suggests unique properties and functional characteristics of their immune system. However, the lack of bat specific reagents, in particular antibodies, has limited our knowledge of bat’s immunity. Using cross-reactive antibodies, we report the phenotypic and functional characterization of T cell subsets, B and NK cells in the fruit-eating bat Pteropus alecto. Our findings indicate the predominance of CD8+ T cells in the spleen from wild-caught bats that may reflect either the presence of viruses in this organ or predominance of this cell subset at steady state. Instead majority of T cells in circulation, lymph nodes and bone marrow (BM) were CD4+ subsets. Interestingly, 40% of spleen T cells expressed constitutively IL-17, IL-22 and TGF-β mRNA, which may indicate a strong bias towards the Th17 and regulatory T cell subsets. Furthermore, the unexpected high number of T cells in bats BM could suggest an important role in T cell development. Finally, mitogenic stimulation induced proliferation and production of effector molecules by bats immune cells. This work contributes to a better understanding of bat’s immunity, opening up new perspectives of therapeutic interventions for humans.

Novel Insights Into Immune Systems of Bats

“…Very few bat-specific antibodies that identify immune cell populations exist. To overcome this obstacle, Martinez Gomez et al and Periasamy et al screened commercially available antibodies for cross-reactivity to cells isolated from blood and primary and secondary lymphoid tissues of P. alecto bats (120,121). Using monoclonal antibodies specific to mammalian transcription factors, Martinez Gomez et al found that wildcaught P. alecto bats displayed a predominance of CD8+ T cells in the spleen, whereas CD4+ T cells were the most prevalent lymphocyte in the blood, lymph nodes, and bone marrow.…”

“…Most studies on bat immune-relevant cells have been carried out on cells from fruit bats. Functional characterization of bat T and B cells have been carried out by detecting cytokines that are secreted by these cells on stimulation (120,121). NK cells from P. alecto and E. spalaea have been detected by flow-cytometry (121).…”

Going to Bat(s) for Studies of Disease Tolerance

“…Given the general absence of clinical signs of disease in bats infected with the same viruses that are so lethal in humans or other non-natural hosts infected experimentally, a critical question has been to understand whether bats might establish effective disease tolerance, thus maintaining fitness despite pathogen replication, or whether bats are more resistant to infection through more successful control of pathogen replication and what the contribution of the immune response is (65,66). The lack of many fundamental immunological tools enabling the probing of bat immune responses has meant that truly mechanistic studies of bat immunity have been very limited, although recently there has been some progress in establishing approaches such as flow cytometry to identify distinct bat immune cell populations (67,68). So far, studies of bat immunity have primarily taken one of three approaches, whereby each comes with important strengths and weaknesses that have to be kept in mind: (i) comparative genome studies, (ii) in vitro cell culture assays, and (iii) experimental infections.…”

Changing resource landscapes and spillover of henipaviruses

“…This allows bats to more specifically and effectively target pathogens, but likely at the expense of immune processes that generate high antibody levels (titers) . In addition, in wild‐caught P. alecto , immune cells called T cells that are classically involved in antiviral responses in other mammals seem to co‐occur with other T cell subsets that regulate immune response . This suggests that cell‐mediated immunity in bats may be biased toward regulatory and anti‐inflammatory processes.…”