Sunday, September 26, 2021

Alterations in Immune Genes Make Bats Great Viral Hosts

Very recommendable! Why do bats not get sick given all the pathogenic and lethal viruses they host? There is something to be learnt here!

"Researchers reported in PNAS yesterday (October 26 [2020]) that various species of bats have slightly different ways of suppressing inflammation, all centered on changes in genes responsible for triggering innate immune responses. ...
The authors demonstrate a number of the mechanisms in bats that seem to support their capacity to tolerate viruses that make other mammals really sick, ... “This follows a series of other publications that really highlight a dampened inflammatory response in bats that suggests that they are uniquely resistant and resilient to the consequences of immunopathology . . . and don’t experience the kind of autoimmune disease that we often incur against ourselves
In a study published in 2013 ... compared the genomes of two bat species: the fruit bat (Pteropus alecto) and insectivorous bat (Myotis davidii). They found that both species had lost a gene called AIM2, which in other mammals encodes a protein that senses pathogenic DNA and triggers inflammasomes ...
In contrast, they found, the Myotis genus of bats has functional caspase-1, but these animals’ genomes instead contain mutations in IL-1β that prevent the cytokine’s cleavage and subsequent for cellular secretion. A third species, the cave nectar bat (Eonycteris spelaea) had diminished, though not completely suppressed, function of both caspase-1 and IL-1β, resulting from a handful of mutations. ..."

From the abstract:
"... Restoration of AIM2 in bat cells led to intact ASC speck formation, but intriguingly resulted in a lack of caspase-1 or consequent IL-1β activation. We further identified two residues undergoing positive selection pressures in Pteropus alecto caspase-1 that abrogate its enzymatic function and are crucial in human caspase-1 activity. Functional analysis of another bat lineage revealed a targeted mechanism for loss of Myotis davidii IL-1β cleavage and elucidated an inverse complementary relationship between caspase-1 and IL-1β, resulting in overall diminished signaling across bats of both suborders. Thus we report strategies that additionally undermine downstream inflammasome signaling in bats, limiting an overactive immune response against pathogens while potentially producing an antiinflammatory state resistant to diseases such as atherosclerosis, aging, and neurodegeneration."

Alterations in Immune Genes Make Bats Great Viral Hosts | The Scientist Magazine® Bat species use different strategies to dampen immune activation in response to viruses.

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