# Functional Characterization of Egyptian rousette Bat Innate immune synapses

> **NIH NIH R21** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $253,500

## Abstract

The long-term goal is to characterize the cellular and molecular constituents of the bat immune system. Our
group had been working on Marburg virus (MARV) spillover and transmission from Egyptian rousette (ERB,
Rousettus aegyptiacus) bats. The ultimate goal of One Health pathogen surveillance programs is the
identification of the most likely source of pathogen spillovers, and the practices more likely to facilitate the barrier
jump. After this, the fate of emergence depends on the pathogen ability to transmit within humans. Our central
hypothesis is that the immunological differences between the zoonotic host and humans are a
significant determinant of the frequency of spillovers. After a detailed genome comparison, we reported
multiple immune-related gene families that have undergone expansion in ERB compared to humans: the
expansion of natural Killer Lectin-like Receptor-C (KLRC or NKG2) and KLR-D (or CD94) gene families, MHC
Class I genes and type I interferon -ω and -α. Later, we revealed an increase in copy number of IGHV genes
known to act in viral protection in humans; a duplication of functional IgE genes with different tissue expression
patterns and theoretical functions; distinctive putative functions and structural characteristics of the four IgGs;
lack of expansion of FcR for IgG (FcγR) compared to primates and potential different functionality; and the
complete absence of functional short pentraxins. All these observations indicate that ERB establishes a
tolerogenic state to deal with pathogen infection. Here, we propose to functionally characterize ERBs
unique NK and IFN immunological synapses. The objective of this proposal is to confirm experimentally the
predicted genomic functionality. The rationale is that Tolerance could be the basis for the unusual resilience of
bats to withstand viral infections that are highly virulent and/or lethal in humans. The central hypothesis will be
tested by pursuing 2 specific aims: 1) To determine the NKG2-CD94 association potential to form a functional
receptor and the signaling downstream of the heterodimers to evaluate ERB NK activation mechanisms.; 2) To
determine functionality and signaling cascade downstream ERBs Type I IFNs to test whether the expansion of
IFN -ω and -α correlates with biological differences. We will pursue them using an innovative combination of
immunological techniques that take advantage from NIAID investments in the Atlas of Immune Cells, and single-
cell genomics as well as previous investments to generate ERB specific reagents. This research is significant,
because it will advance knowledge at the crucial interphase that determine transmission and pathogenesis if the
differences between the immunological status of different mammals are a driver for zoonotic spillovers. The
proximate expected outcome of this work is an understanding of the particularities of the bat innate
immunological system and an assessment of its baseline status. The results will have an immediat...

## Key facts

- **NIH application ID:** 10451027
- **Project number:** 1R21AI169535-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Gustavo F. Palacios
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $253,500
- **Award type:** 1
- **Project period:** 2022-02-18 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10451027

## Citation

> US National Institutes of Health, RePORTER application 10451027, Functional Characterization of Egyptian rousette Bat Innate immune synapses (1R21AI169535-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10451027. Licensed CC0.

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