Constitutive IFNα protein production in bats

Abstract

Bats are the only mammals with self-powered flight and account for 20% of all extant mammalian diversity. In addition, they harbor many emerging and reemerging viruses, including multiple coronaviruses, several of which are highly pathogenic in other mammals, but cause no disease in bats. How this relationship between bats and viruses exists is not yet fully understood. Existing evidence supports a specific role for the innate immune system, in particular type I interferon (IFN) responses, a major component of antiviral immunity. Previous studies in bats have shown that components of the IFN pathway are constitutively activated at the transcriptional level. In this study, we tested the hypothesis that the type I IFN response in bats is also constitutively activated at the protein level. For this we utilized highly sensitive Single Molecule (Simoa) digital ELISA assays, previously developed for humans that we adapted to bat samples. We prospectively sampled four non-native chiroptera species from French zoos. We identified a constitutive expression of IFNα protein in the circulation of healthy bats, and concentrations that are physiologically active in humans. Expression levels differed according to the species examined, but was not associated with age, sex, or health status suggesting constitutive IFNα protein expression independent of disease. These results confirm a unique IFN response in bat species that may explain their ability to coexist with multiple viruses in the absence of pathology. These results may help to manage potential zoonotic viral reservoirs and potentially identify new anti-viral strategies.

Serum Proteomics Identifies Immune Pathways and Candidate Biomarkers of Coronavirus Infection in Wild Vampire Bats

“…This tolerance of otherwise virulent infections is likely driven by distinct aspects of bat immunity that evolved alongside their unique ability of powered flight and their very long lifespans (12)(13)(14). These include but are not limited to constitutive expression of interferons (IFNs) and IFNstimulated genes (ISGs), robust complement proteins, and a dampened inflammatory response (15)(16)(17)(18)(19)(20).…”

Landscape and age dynamics of immune cells in the Egyptian rousette bat

“…Bats detect and respond to RNA viruses, while DNA sensing is dampened, due to limited signaling via stimulator of interferon genes (STING) (Xie et al, 2018), absence of members of the pyrin and hematopoietic interferon-inducible nuclear (HIN) domain (PYHIN) (Zhang et al, 2013) gene family, and short pentraxins (Larson et al, 2021). Interestingly, interferon (IFN) expression is constitutive in steady state in several bat species (Bondet et al, 2021;Zhou et al, 2016b). Moreover, inflammation appears to be restricted, as shown by reduced activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome (Ahn et al, 2019) and limited bioactive interleukin (IL)-1b secretion (Ahn et al, 2019;Goh et al, 2020).…”

Serum proteomics identifies immune pathways and candidate biomarkers of coronavirus infection in wild vampire bats

“…This tolerance of otherwise virulent infections is likely driven by distinct aspects of bat immunity that evolved alongside their unique ability of powered flight and their very long lifespans (Wilkinson and South, 2002; Zhang et al, 2013; Irving et al, 2021). These include but are not limited to constitutive expression of interferons (IFNs) and IFN-stimulated genes (ISGs), robust complement proteins, and a dampened inflammatory response (Zhou et al, 2016; Ahn et al, 2019; Becker et al, 2019; Banerjee et al, 2020; Jebb et al, 2020; Bondet et al, 2021).…”