Serum proteomics reveals a tolerant immune phenotype across multiple pathogen taxa in wild vampire bats

Abstract

Bats carry many zoonotic pathogens without showing pronounced pathology, with a few exceptions. The underlying immune tolerance mechanisms in bats remain poorly understood, although information-rich omics tools hold promise for identifying a wide range of immune markers and their relationship with infection. To evaluate the generality of immune responses to infection, we assessed the differences and similarities in serum proteomes of wild vampire bats (Desmodus rotundus) across infection status with five taxonomically distinct pathogens: bacteria (Bartonella spp., hemoplasmas), protozoa (Trypanosoma cruzi), and DNA (herpesviruses) and RNA (alphacoronaviruses) viruses. From 19 bats sampled in 2019 in Belize, we evaluated the up- and downregulated immune responses of infected versus uninfected individuals for each pathogen. Using a high-quality genome annotation for vampire bats, we identified 586 serum proteins but found no evidence for differential abundance nor differences in composition between infected and uninfected bats. However, using receiver operating characteristic curves, we identified four to 48 candidate biomarkers of infection depending on the pathogen, including seven overlapping biomarkers (DSG2, PCBP1, MGAM, APOA4, DPEP1, GOT1, and IGFALS). Enrichment analysis of these proteins revealed that our viral pathogens, but not the bacteria or protozoa studied, were associated with upregulation of extracellular and cytoplasmatic secretory vesicles (indicative of viral replication) and downregulation of complement activation and coagulation cascades. Additionally, herpesvirus infection elicited a downregulation of leukocyte-mediated immunity and defense response but an upregulation of an inflammatory and humoral immune response. In contrast to our two viral infections, we found downregulation of lipid and cholesterol homeostasis and metabolism with Bartonella spp. infection, of platelet-dense and secretory granules with hemoplasma infection, and of blood coagulation pathways with T. cruzi infection. Despite the small sample size, our results suggest that vampire bats have a similar suite of immune mechanisms for viruses distinct from responses to the other pathogen taxa, and we identify potential biomarkers that can expand our understanding of pathogenesis of these infections in bats. By applying a proteomic approach to a multi-pathogen system in wild animals, our study provides a distinct framework that could be expanded across bat species to increase our understanding of how bats tolerate pathogens.

Geographically widespread and novel hemotropic mycoplasmas and bartonellae in Mexican free-tailed bats and sympatric North American bat species

“…Other -omics analyses could also elucidate whether these bacterial infections are pathogenic in bats themselves. In addition to assessing impacts of infection on migration outcomes as noted above, approaches such as transcriptomics and proteomics could test if bats have a pronounced immune response to these bacterial infections or appear largely tolerant (47). Such studies could be especially informative when comparing immunity between migratory and non-migratory periods, which could test whether long-distance migration may disrupt immune tolerance in bats.…”

Advances in understanding bat infection dynamics across biological scales

“…Transcriptomic approaches, in which a snapshot of expressed genes is sequenced and identified, have proven invaluable in understanding the severity of metabolic and immune consequences of infection for bats [ 15 , 43 , 44 ]. Additionally, the blood proteome contains proteins secreted from blood cells and organs, including those involved in host response to infection and immune biomarkers, and innovative proteomic tools show potential in characterizing bat immune systems and their responses to microbial infections [ 45 ]. Complemented by recent advances in genomics [ 46 ], ‘-omics’ approaches stand to further our ability to explore mechanisms by which bats interact with microbes and consequences for bat physiological status.…”