Exploring the Role of Innate Lymphocytes in the Immune System of Bats and Virus-Host Interactions

Abstract

Bats are reservoirs of a large number of viruses of global public health significance, including the ancestral virus for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the causative agent of coronavirus disease 2019 (COVID-19). Although bats are natural carriers of multiple pathogenic viruses, they rarely display signs of disease. Recent insights suggest that bats have a more balanced host defense and tolerance system to viral infections that may be linked to the evolutionary adaptation to powered flight. Therefore, a deeper understanding of bat immune system may provide intervention strategies to prevent zoonotic disease transmission and to identify new therapeutic targets. Similar to other eutherian mammals, bats have both innate and adaptive immune systems that have evolved to detect and respond to invading pathogens. Bridging these two systems are innate lymphocytes, which are highly abundant within circulation and barrier tissues. These cells share the characteristics of both innate and adaptive immune cells and are poised to mount rapid effector responses. They are ideally suited as the first line of defense against early stages of viral infections. Here, we will focus on the current knowledge of innate lymphocytes in bats, their function, and their potential role in host–pathogen interactions. Moreover, given that studies into bat immune systems are often hindered by a lack of bat-specific research tools, we will discuss strategies that may aid future research in bat immunity, including the potential use of organoid models to delineate the interplay between innate lymphocytes, bat viruses, and host tolerance.

In vitro high-content tissue models to address precision medicine challenges

“…These models have been suggested as a prominent platform to gain a fundamental understanding of viral infections such as COVID-19 ( Basanthakumar, 2021 ; de Melo et al, 2021 ; Deguchi et al, 2021 ; Harb et al, 2022 ; Kronemberger et al, 2021 ; Lv et al, 2021 ; Ramani et al, 2021 ; Sia et al, 2022 ; Sourimant et al, 2022 ; van der Vaart et al, 2021 ; Wang et al; Yu, 2021 ; Zech et al, 2021 ) and could be a good alternative to facilitate the development and discovery of new therapeutics and vaccines ( Clevers, 2020 ; Raimondi et al, 2020 ). To date, various types of organoid-enabled 3D models have been employed to study and understand SARS-CoV-2 infection such as the brain organoid ( Ramani et al, 2020 ), lung organoid ( Ekanger et al, 2022 ; Salahudeen et al, 2020 ; van der Vaart et al, 2021 ; Wang et al, 2021a ), intestine organoid ( Dickson, 2020 ), as well as liver ductal organoid and bile duct organoid ( Zhao et al, 2020a ) ( Fig.…”

Genes, inflammatory response, tolerance, and resistance to virus infections in migratory birds, bats, and rodents

“…However, the innate and adaptive immune systems that detect and respond to invading pathogens in eutherian mammals must be integrated to guarantee efficient protection. The role of integrating these two systems in both bats and humans belongs to the lymphocytes of the innate immune response, which share both adaptive and innate features, and are abundant in the peripheral circulation and in barrier tissues ( 192 , 193 ).…”

“…However, the innate and adaptive immune systems that detect and respond to invading pathogens in eutherian mammals must be Frontiers in Immunology frontiersin.org integrated to guarantee efficient protection. The role of integrating these two systems in both bats and humans belongs to the lymphocytes of the innate immune response, which share both adaptive and innate features, and are abundant in the peripheral circulation and in barrier tissues (192,193). Innate lymphocytes ("unconventional" or "innate-like T cells"), including innate lymphoid cells, natural killer cells, ɣd T cells and mucosal-associated invariant T cells (194), were detected in a number of bat species (192).…”

An overview of bats microbiota and its implication in transmissible diseases

“…Also, intestinal microbiota is an important player in health and disease (Fan and Pedersen, 2021). In bats, immunological tolerance has been observed against viral infections (Guito et al, 2021;Irving et al, 2021;Sia et al, 2022). In this case, the Federici et al 10.3389/fmicb.2022.1012189 Frontiers in Microbiology 16 frontiersin.org immune response is not directed primarily against the pathogen through an inflammatory response, but instead at limiting host tissue damage caused by pathogen and activating tissue repair mechanisms.…”