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Written by | Xiaofeifei multicellular organisms and mucosal surfaces are usually colonized with specific groups of symbiotic microorganisms, known as microbiota, which can also affect some pathophysiological processes of the host [
Most of these microorganisms are obligate extracellular bacteria that colonize the g.
On the one hand, these microorganisms play an important role in the development and maturation of the host immune system; on the other hand, they can also protect the host from infection by some bacteria by competing with some bacteria and fungi for nutrients and living space or by producing antibacterial substances [
However, how the microbiota affects viral infection is still unclear, and whether the microbiota can promote or inhibit the body's antiviral immune response under different research backgrounds is still inconclusi.
Type I interferons (IFN-Is) play an important role in the body's antiviral immuni.
During the infection process, the body will produce a large amount of IFN-Is, but the body will also produce a small amount of IFN-Is in a resting sta.
The production of these basal levels of IFN-Is enables the immune system to maintain an alert state to respond effectively to infection and other danger signals [
IFN-Is are usually induced by three main innate immune pathways: Toll-like receptors (TLRs) on the cytoplasmic or endosomal membrane [4], and intracellular RIG-I-like recepto.
Rig-I-like receptors (RLRs) RNA recognition pathway [5], and the cytoplasmic DNA recognition pathway cGAS/STING [
Over the past decade, numerous studies have shown that the microbiota plays a role in the induction of IFN-Is producti.
At present, the role of TLRs is mainly focused on how the microbiota induces the production of IFN-Is, and there are contradictory conclusio.
For example, some studies have shown that the production of IFN-Is by the microbiota is due to the activation of TLR4 by bacterial glycolipids [7], while other studies have shown that bacterial metabolites activate TLR7 to promote IFN-I production, while other TLRs do not [8] that wor.
Other studies have shown that the deletion of universal adaptor proteins downstream of TLRs did not lead to a reduction in basal IFN-Is levels [
Therefore, which innate immune receptors are involved in sensing the microbiota and promoting the production of IFN-Is remains unkno.
In addition, on the surface of the barrier between the body and the outside world, how these obligate extracellular microorganisms communicate with remote immune cells to play a systemic immune regulation role also needs to be studi.
On May 10, 2022, the team of Nelson.
Gekara from Umea˚ University in Sweden published an article on Immunity entitled The gut microbiota primes systemic antiviral immunity via the cGAS-STING-IFN-I axis, which was achieved by a series of gene knockou.
In mice, it was found that the intestinal flora maintains the basal level of IFN-I production in the resting state by activating the body's cGAS-STING signaling pathway, which plays an important role in the body's resistance to DNA and RNA virus infecti.
Activation of cGAS-STING-IFN-I by this microbiota does not require direct interaction of host bacteria, but rather remote transport of bacterial DNA into host cells via bacterial-derived membrane vesicl.
Sometimes people take some antibiotics themselves to treat some diseas.
Some doctors also prescribe antibiotics to some people with viral infections to prevent bacterial infections that often accompany viral infectio.
However, the use of antibiotics can affect the intestinal flora, and whether the use of these antibiotics affects recovery from viral infections is a question worth investigati.
To study this process, the researchers gave mice a combination of antibiotics such as ampicillin, neomycin and vancomycin oral.
Sequencing the 16S rDNA of the mouse feces two weeks later found that the antibiotic treatment did significantly reduce the abundance of the mice's gut bacter.
Subsequently, mice were infected with the DNA virus herpes simplex virus type 1 (HSV-1) in the lungs or systemically by intranasal or intraperitoneal injection, and it was found that the antibiotic-treated mice had higher viral replication and more severe clinical sympto.
This suggests that commensal bacteria in the gut can promote antiviral responses in the body, including in distant orga.
Basal levels of IFN-Is play an important role in the body's resistance to viral infecti.
To explore whether the aggravation of viral infection by antibiotic use is related to the activation of IFN-Is by commensal bacteria, the researchers used Ifnb1 luciferase reporter mice (Ifnb+/Δβ-luc) to monitor the levels of IFN-.
It was found that antibiotic treatment led to a decrease in the systemic basal levels of IFN-I and the expression of interferon-stimulated genes and pro-inflammatory cytokines in the tissues of mice in the resting state, which may be the reason why antibiotics inhibit the body's antiviral respon.
The interaction between gut symbionts and the host needs to be well regulated to maintain a mutually beneficial symbiotic relationship between gut symbionts and the host and avoid pathological immune respons.
For example, the intestinal mucosal layer provides physical isolati.
Furthermore, to avoid hyperactivation by the gut microbiota, gut epithelial cells either express very low levels of TLRs or only express TLRs outside the base not facing the bacteria, and TLRs signaling in intestinal epidermal cells is highly inhibit.
Unlike pathogenic bacteria, commensal bacteria are generally avirulent and do not breach the host mucosal barrier to penetrate deep into tissue and immune cel.
More importantly, symbionts often produce modified microbe-associated molecular patterns that inhibit rather than activate TLRs signali.
Despite so many host- and microbe-related factors, how can commensal bacteria at the far end of the host barrier elicit a systemic IFN-Is response in the body against viral infection? In addition, which innate immune signaling pathway is involved? To investigate this issue, the researchers next knocked out a series of IFN-Is-produced innate immune pathway signaling proteins in Ifnb1-luciferase reporter mice, and observed their effects on resting basal levels of IFN-Is producti.
It was found that the knockdown of the adaptor proteins TRIF and MYD88 downstream of TLRs did not affect the production of basal levels of IFN-Is, and further knockdown of MAVS downstream of RLRs also had little effect on the production of basal levels of IFN-Is, while the knockout of STING significantly reduced the production of IFN-.
production of basal levels of IFN-.
Following antibiotic treatment, fecal transplantation restored basal IFN-Is levels in wild-type mice, but not in STING knockout mi.
This suggests that the intracellular STING signaling pathway is required for the production of IFN-Is by the gut microbio.
Subsequently, the researchers found that these intestinal obligate extracellular commensal bacteria do not require direct contact with immune cells to activate STING-IFN-Is, but activate STING-IFN through bacterially secreted membrane vesicles (MV.
-Is signaling improves the body's ability to resist viral infection
It was further found that bacterial membrane vesicles encapsulate bacterial DNA to prevent it from being degraded by nucleases, and transmit it to distant immune cells to activate cGAS-STING-IFN-Is signaling in cells to maintain the resting sta.
levels of interferon producti.
Bacterial membrane vesicles encapsulating bacterial DNA were also detected in the circulatory system of mi.
Moreover, the gut microbiota can also help the body to resist the infection of RNA virus vesicular stomatitis virus (VSV) through cAGS/STING-mediated basal IFN-Is production, similar to antibiotic-treated mice, cGAS or STING The levels of basal IFN-Is were significantly decreased in knockout mice, whereas virus clearance was slower after VSV infecti.
In conclusion, the present study shows that the gut microbiota may transmit bacterial DNA to distant immune cells through bacterial microvesicles, activate cGAS-STING-IFN-Is signaling in cells, and activate cGAS-STING-IFN-Is signaling through multiple mouse models combined with in vivo and in vitro experimen.
Maintaining a certain basal level of type I interferon can improve the body's ability to deal with viral infection, which also implies that the abuse of antibiotics may affect the risk of increasing viral infecti.
Original link: https://d.
org/11016.
immu.
2020006 Publisher: Eleven ReferencesBlander, JM, et .
, Regulation of inflammation by microbiota interactions with the ho.
Nature Immunology, 201 18(8):.
851-86 Khosravi,.
and SK Mazmanian, Disruption of the gut microbiome as a risk factor for microbial infectio.
Current Opinion in Microbiology, 201 16(2):.
221- 22 Gough, Daniel.
, et .
, Constitutive Type I Interferon Modulates Homeostatic Balance through Tonic Signali.
Immunity, 201 36(2):.
166-17 Kawai,.
and.
Akira, Toll-like Receptors and Their Crosstalk with Other Innate Receptors in Infection and Immuni.
Immunity, 201 34(5):.
637-65 Loo,.
.
and.
Gale, Immune Signaling by RIG-I-like Recepto.
Immunity, 201 34(5):.
680-69 Sun,.
, et .
,Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathw.
Science, 201 339(6121):.
786-79 Stefan, KL, et .
, Commensal Microbiota Modulation of Natural Resistance to Virus Infectio.
Cell, 202 183(5):.
1312-132e1 Winkler, ES, et .
, The Intestinal Microbiome Restricts Alphavirus Infection and Dissemination through a Bile Acid-Type I IFN Signaling Ax.
Cell, 202
182(4):.
901-91e1 Schaupp,.
, et .
, Microbiota-Induced Type I Interferons Instruct a Poised Basal State of Dendritic Cel.
Cell, 202 181(5): .
1080-109e1 Instructions for reprinting [Original article] BioArt original articles are welcome to forward and share, and reprinting is prohibited without permissi.
The copyright of all works published is owned by BioArt1312-132e1 Winkler, ES, et .
, The Intestinal Microbiome Restricts Alphavirus Infection and Dissemination through a Bile Acid-Type I IFN Signaling Ax.
Cell, 202 182(4):.
901-91 e1 Schaupp,.
, et .
, Microbiota-Induced Type I Interferons Instruct a Poised Basal State of Dendritic Cel.
Cell, 202 181(5):.
1080-109e1 Notes for reprinting [Original article 】BioArt original articles, personal reposting and sharing are welcome, reprinting is prohibited without permission, and the copyright of all published works is owned by BioArt1312-132e1 Winkler, ES, et .
, The Intestinal Microbiome Restricts Alphavirus Infection and Dissemination through a Bile Acid-Type I IFN Signaling Ax.
Cell, 202 182(4):.
901-91 e1 Schaupp,.
, et .
, Microbiota-Induced Type I Interferons Instruct a Poised Basal State of Dendritic Cel.
Cell, 202 181(5):.
1080-109e1 Notes for reprinting [Original article 】BioArt original articles, personal reposting and sharing are welcome, reprinting is prohibited without permission, and the copyright of all published works is owned by BioArt
BioArt reserves all legal rights and violators will be held accountab.
Most of these microorganisms are obligate extracellular bacteria that colonize the g.
On the one hand, these microorganisms play an important role in the development and maturation of the host immune system; on the other hand, they can also protect the host from infection by some bacteria by competing with some bacteria and fungi for nutrients and living space or by producing antibacterial substances [
However, how the microbiota affects viral infection is still unclear, and whether the microbiota can promote or inhibit the body's antiviral immune response under different research backgrounds is still inconclusi.
Type I interferons (IFN-Is) play an important role in the body's antiviral immuni.
During the infection process, the body will produce a large amount of IFN-Is, but the body will also produce a small amount of IFN-Is in a resting sta.
The production of these basal levels of IFN-Is enables the immune system to maintain an alert state to respond effectively to infection and other danger signals [
IFN-Is are usually induced by three main innate immune pathways: Toll-like receptors (TLRs) on the cytoplasmic or endosomal membrane [4], and intracellular RIG-I-like recepto.
Rig-I-like receptors (RLRs) RNA recognition pathway [5], and the cytoplasmic DNA recognition pathway cGAS/STING [
Over the past decade, numerous studies have shown that the microbiota plays a role in the induction of IFN-Is producti.
At present, the role of TLRs is mainly focused on how the microbiota induces the production of IFN-Is, and there are contradictory conclusio.
For example, some studies have shown that the production of IFN-Is by the microbiota is due to the activation of TLR4 by bacterial glycolipids [7], while other studies have shown that bacterial metabolites activate TLR7 to promote IFN-I production, while other TLRs do not [8] that wor.
Other studies have shown that the deletion of universal adaptor proteins downstream of TLRs did not lead to a reduction in basal IFN-Is levels [
Therefore, which innate immune receptors are involved in sensing the microbiota and promoting the production of IFN-Is remains unkno.
In addition, on the surface of the barrier between the body and the outside world, how these obligate extracellular microorganisms communicate with remote immune cells to play a systemic immune regulation role also needs to be studi.
On May 10, 2022, the team of Nelson.
Gekara from Umea˚ University in Sweden published an article on Immunity entitled The gut microbiota primes systemic antiviral immunity via the cGAS-STING-IFN-I axis, which was achieved by a series of gene knockou.
In mice, it was found that the intestinal flora maintains the basal level of IFN-I production in the resting state by activating the body's cGAS-STING signaling pathway, which plays an important role in the body's resistance to DNA and RNA virus infecti.
Activation of cGAS-STING-IFN-I by this microbiota does not require direct interaction of host bacteria, but rather remote transport of bacterial DNA into host cells via bacterial-derived membrane vesicl.
Sometimes people take some antibiotics themselves to treat some diseas.
Some doctors also prescribe antibiotics to some people with viral infections to prevent bacterial infections that often accompany viral infectio.
However, the use of antibiotics can affect the intestinal flora, and whether the use of these antibiotics affects recovery from viral infections is a question worth investigati.
To study this process, the researchers gave mice a combination of antibiotics such as ampicillin, neomycin and vancomycin oral.
Sequencing the 16S rDNA of the mouse feces two weeks later found that the antibiotic treatment did significantly reduce the abundance of the mice's gut bacter.
Subsequently, mice were infected with the DNA virus herpes simplex virus type 1 (HSV-1) in the lungs or systemically by intranasal or intraperitoneal injection, and it was found that the antibiotic-treated mice had higher viral replication and more severe clinical sympto.
This suggests that commensal bacteria in the gut can promote antiviral responses in the body, including in distant orga.
Basal levels of IFN-Is play an important role in the body's resistance to viral infecti.
To explore whether the aggravation of viral infection by antibiotic use is related to the activation of IFN-Is by commensal bacteria, the researchers used Ifnb1 luciferase reporter mice (Ifnb+/Δβ-luc) to monitor the levels of IFN-.
It was found that antibiotic treatment led to a decrease in the systemic basal levels of IFN-I and the expression of interferon-stimulated genes and pro-inflammatory cytokines in the tissues of mice in the resting state, which may be the reason why antibiotics inhibit the body's antiviral respon.
The interaction between gut symbionts and the host needs to be well regulated to maintain a mutually beneficial symbiotic relationship between gut symbionts and the host and avoid pathological immune respons.
For example, the intestinal mucosal layer provides physical isolati.
Furthermore, to avoid hyperactivation by the gut microbiota, gut epithelial cells either express very low levels of TLRs or only express TLRs outside the base not facing the bacteria, and TLRs signaling in intestinal epidermal cells is highly inhibit.
Unlike pathogenic bacteria, commensal bacteria are generally avirulent and do not breach the host mucosal barrier to penetrate deep into tissue and immune cel.
More importantly, symbionts often produce modified microbe-associated molecular patterns that inhibit rather than activate TLRs signali.
Despite so many host- and microbe-related factors, how can commensal bacteria at the far end of the host barrier elicit a systemic IFN-Is response in the body against viral infection? In addition, which innate immune signaling pathway is involved? To investigate this issue, the researchers next knocked out a series of IFN-Is-produced innate immune pathway signaling proteins in Ifnb1-luciferase reporter mice, and observed their effects on resting basal levels of IFN-Is producti.
It was found that the knockdown of the adaptor proteins TRIF and MYD88 downstream of TLRs did not affect the production of basal levels of IFN-Is, and further knockdown of MAVS downstream of RLRs also had little effect on the production of basal levels of IFN-Is, while the knockout of STING significantly reduced the production of IFN-.
production of basal levels of IFN-.
Following antibiotic treatment, fecal transplantation restored basal IFN-Is levels in wild-type mice, but not in STING knockout mi.
This suggests that the intracellular STING signaling pathway is required for the production of IFN-Is by the gut microbio.
Subsequently, the researchers found that these intestinal obligate extracellular commensal bacteria do not require direct contact with immune cells to activate STING-IFN-Is, but activate STING-IFN through bacterially secreted membrane vesicles (MV.
-Is signaling improves the body's ability to resist viral infection
It was further found that bacterial membrane vesicles encapsulate bacterial DNA to prevent it from being degraded by nucleases, and transmit it to distant immune cells to activate cGAS-STING-IFN-Is signaling in cells to maintain the resting sta.
levels of interferon producti.
Bacterial membrane vesicles encapsulating bacterial DNA were also detected in the circulatory system of mi.
Moreover, the gut microbiota can also help the body to resist the infection of RNA virus vesicular stomatitis virus (VSV) through cAGS/STING-mediated basal IFN-Is production, similar to antibiotic-treated mice, cGAS or STING The levels of basal IFN-Is were significantly decreased in knockout mice, whereas virus clearance was slower after VSV infecti.
In conclusion, the present study shows that the gut microbiota may transmit bacterial DNA to distant immune cells through bacterial microvesicles, activate cGAS-STING-IFN-Is signaling in cells, and activate cGAS-STING-IFN-Is signaling through multiple mouse models combined with in vivo and in vitro experimen.
Maintaining a certain basal level of type I interferon can improve the body's ability to deal with viral infection, which also implies that the abuse of antibiotics may affect the risk of increasing viral infecti.
Original link: https://d.
org/11016.
immu.
2020006 Publisher: Eleven ReferencesBlander, JM, et .
, Regulation of inflammation by microbiota interactions with the ho.
Nature Immunology, 201 18(8):.
851-86 Khosravi,.
and SK Mazmanian, Disruption of the gut microbiome as a risk factor for microbial infectio.
Current Opinion in Microbiology, 201 16(2):.
221- 22 Gough, Daniel.
, et .
, Constitutive Type I Interferon Modulates Homeostatic Balance through Tonic Signali.
Immunity, 201 36(2):.
166-17 Kawai,.
and.
Akira, Toll-like Receptors and Their Crosstalk with Other Innate Receptors in Infection and Immuni.
Immunity, 201 34(5):.
637-65 Loo,.
.
and.
Gale, Immune Signaling by RIG-I-like Recepto.
Immunity, 201 34(5):.
680-69 Sun,.
, et .
,Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathw.
Science, 201 339(6121):.
786-79 Stefan, KL, et .
, Commensal Microbiota Modulation of Natural Resistance to Virus Infectio.
Cell, 202 183(5):.
1312-132e1 Winkler, ES, et .
, The Intestinal Microbiome Restricts Alphavirus Infection and Dissemination through a Bile Acid-Type I IFN Signaling Ax.
Cell, 202
182(4):.
901-91e1 Schaupp,.
, et .
, Microbiota-Induced Type I Interferons Instruct a Poised Basal State of Dendritic Cel.
Cell, 202 181(5): .
1080-109e1 Instructions for reprinting [Original article] BioArt original articles are welcome to forward and share, and reprinting is prohibited without permissi.
The copyright of all works published is owned by BioArt1312-132e1 Winkler, ES, et .
, The Intestinal Microbiome Restricts Alphavirus Infection and Dissemination through a Bile Acid-Type I IFN Signaling Ax.
Cell, 202 182(4):.
901-91 e1 Schaupp,.
, et .
, Microbiota-Induced Type I Interferons Instruct a Poised Basal State of Dendritic Cel.
Cell, 202 181(5):.
1080-109e1 Notes for reprinting [Original article 】BioArt original articles, personal reposting and sharing are welcome, reprinting is prohibited without permission, and the copyright of all published works is owned by BioArt1312-132e1 Winkler, ES, et .
, The Intestinal Microbiome Restricts Alphavirus Infection and Dissemination through a Bile Acid-Type I IFN Signaling Ax.
Cell, 202 182(4):.
901-91 e1 Schaupp,.
, et .
, Microbiota-Induced Type I Interferons Instruct a Poised Basal State of Dendritic Cel.
Cell, 202 181(5):.
1080-109e1 Notes for reprinting [Original article 】BioArt original articles, personal reposting and sharing are welcome, reprinting is prohibited without permission, and the copyright of all published works is owned by BioArt
BioArt reserves all legal rights and violators will be held accountab.
