Intestinal microbiota programming of alveolar macrophages influences severity of respiratory viral infection.
Susceptibility to respiratory virus infections (RVIs) varies widely across individuals. Because the gut microbiome impacts immune function, we investigated the influence of intestinal microbiota composition on RVI and determined that segmented filamentous bacteria (SFB), naturally acquired or exogenously administered, protected mice against influenza virus (IAV) infection. Such protection, which also applied to respiratory syncytial virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was independent of interferon and adaptive immunity but required basally resident alveolar macrophages (AMs). In SFB-negative mice, AMs were quickly depleted as RVI progressed. In contrast, AMs from SFB-colonized mice were intrinsically altered to resist IAV-induced depletion and inflammatory signaling. Yet, AMs from SFB-colonized mice were not quiescent. Rather, they directly disabled IAV via enhanced complement production and phagocytosis. Accordingly, transfer of SFB-transformed AMs into SFB-free hosts recapitulated SFB-mediated protection against IAV. These findings uncover complex interactions that mechanistically link the intestinal microbiota with AM functionality and RVI severity.
Pubmed ID: 38295788 RIS Download
Research resources used in this publication
- Tac:SW (RRID:IMSR_TAC:SW) (organism)
-
NOD.Cg-Rag1tm1Mom Il2rg
- B6(Cg)-C1qatm1d(EUCOMM)Wtsi/TennJ (RRID:IMSR_JAX:031675) (organism)
- B6.129S(Cg)-Stat1tm1Dlv/J (RRID:IMSR_JAX:012606) (organism)
- B6.129S7-Rag1tm1Mom/J (RRID:IMSR_JAX:002216) (organism)
- B6.129S-Csf2tm1Mlg/J (RRID:IMSR_JAX:026812) (organism)
- B6.129S(C)-Batf3tm1Kmm/J (RRID:IMSR_JAX:013755) (organism)
- C57BL/6J (RRID:IMSR_JAX:000664) (organism)
- B6.129S2-Ifnar1tm1Agt/Mmjax (RRID:MMRRC_032045-JAX) (organism)
Additional research tools detected in this publication
None foundAntibodies used in this publication
- Alexa Fluor(R) 700 anti-mouse CD326 (Ep-CAM) (RRID:AB_2810354)
- C1QA Polyclonal Antibody (RRID:AB_2547062)
- APC anti-mouse CD31 (RRID:AB_312917)
- PE anti-mouse Podoplanin (RRID:AB_2161928)
- CD45.2 (RRID:AB_10894189)
- CD45.1 Monoclonal Antibody (A20), PE-Cyanine7, eBioscience (RRID:AB_469629)
- Ms CD200 PE OX-90 50ug (RRID:AB_2869684)
- APC anti-mouse CD86 (RRID:AB_493342)
- FceR1 alpha Monoclonal Antibody (MAR-1), APC, eBioscience (RRID:AB_10717073)
- PE-CF594 Rat Anti-Mouse Siglec-F Antibody (RRID:AB_2687994)
- Brilliant Violet 510(TM) anti-mouse CD117 (c-kit) (RRID:AB_2562011)
- Rat Anti-CD24 Monoclonal Antibody, FITC Conjugated, Clone M1/69 (RRID:AB_394740)
- Brilliant Violet 421(TM) anti-mouse CD64 (FcgammaRI) (RRID:AB_2562694)
- I-A/I-E (RRID:AB_2738192)
- CD11c (RRID:AB_2738394)
- Rat Anti-CD11b Monoclonal Antibody, APC-Cy7 Conjugated, Clone M1/70 (RRID:AB_396772)
- Ly-6C Monoclonal Antibody (HK1.4), PerCP-Cyanine5.5, eBioscience(TM) (RRID:AB_1518762)
- Ly-6G (RRID:AB_10611860)
- Brilliant Violet 605(TM) anti-mouse CD45 (RRID:AB_2650656)
Associated grants
- Agency: NIAID NIH HHS, United States
Id: R01 AI141222 - Agency: NIAID NIH HHS, United States
Id: R01 AI170014 - Agency: NIAID NIH HHS, United States
Id: U19 AI171403
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This is a list of tools and resources that we have found mentioned in this publication.
Alexa Fluor(R) 700 anti-mouse CD326 (Ep-CAM) (antibody)
RRID:AB_2810354
This monoclonal targets CD326
View all literature mentionsC1QA Polyclonal Antibody (antibody)
RRID:AB_2547062
This unknown targets C1QA
View all literature mentionsAPC anti-mouse CD31 (antibody)
RRID:AB_312917
This monoclonal targets CD31
View all literature mentionsPE anti-mouse Podoplanin (antibody)
RRID:AB_2161928
This monoclonal targets Podoplanin
View all literature mentionsCD45.1 Monoclonal Antibody (A20), PE-Cyanine7, eBioscience (antibody)
RRID:AB_469629
This monoclonal targets CD45.1
View all literature mentionsMs CD200 PE OX-90 50ug (antibody)
RRID:AB_2869684
This monoclonal targets CD200
View all literature mentionsAPC anti-mouse CD86 (antibody)
RRID:AB_493342
This monoclonal targets CD86
View all literature mentionsFceR1 alpha Monoclonal Antibody (MAR-1), APC, eBioscience (antibody)
RRID:AB_10717073
This monoclonal targets FceR1 alpha
View all literature mentionsPE-CF594 Rat Anti-Mouse Siglec-F Antibody (antibody)
RRID:AB_2687994
This monoclonal targets Siglec-F
View all literature mentionsBrilliant Violet 510(TM) anti-mouse CD117 (c-kit) (antibody)
RRID:AB_2562011
This monoclonal targets CD117
View all literature mentionsRat Anti-CD24 Monoclonal Antibody, FITC Conjugated, Clone M1/69 (antibody)
RRID:AB_394740
This monoclonal targets CD24
View all literature mentionsBrilliant Violet 421(TM) anti-mouse CD64 (FcgammaRI) (antibody)
RRID:AB_2562694
This monoclonal targets CD64
View all literature mentionsRat Anti-CD11b Monoclonal Antibody, APC-Cy7 Conjugated, Clone M1/70 (antibody)
RRID:AB_396772
This monoclonal targets CD11b
View all literature mentionsLy-6C Monoclonal Antibody (HK1.4), PerCP-Cyanine5.5, eBioscience(TM) (antibody)
RRID:AB_1518762
This monoclonal targets Ly-6C
View all literature mentionsBrilliant Violet 605(TM) anti-mouse CD45 (antibody)
RRID:AB_2650656
This monoclonal targets CD45
View all literature mentionsTac:SW (organism)
RRID:IMSR_TAC:SW
Mus musculus with name Tac:SW from IMSR.
View all literature mentions
NOD.Cg-Rag1tm1Mom Il2rg/SzJ (organism)
RRID:IMSR_JAX:007799
Mus musculus with name NOD.Cg-Rag1tm1Mom Il2rg
B6(Cg)-C1qatm1d(EUCOMM)Wtsi/TennJ (organism)
RRID:IMSR_JAX:031675
Mus musculus with name B6(Cg)-C1qatm1d(EUCOMM)Wtsi/TennJ from IMSR.
View all literature mentionsB6.129S(Cg)-Stat1tm1Dlv/J (organism)
RRID:IMSR_JAX:012606
Mus musculus with name B6.129S(Cg)-Stat1tm1Dlv/J from IMSR.
View all literature mentionsB6.129S7-Rag1tm1Mom/J (organism)
RRID:IMSR_JAX:002216
Mus musculus with name B6.129S7-Rag1tm1Mom/J from IMSR.
View all literature mentionsB6.129S-Csf2tm1Mlg/J (organism)
RRID:IMSR_JAX:026812
Mus musculus with name B6.129S-Csf2tm1Mlg/J from IMSR.
View all literature mentionsB6.129S(C)-Batf3tm1Kmm/J (organism)
RRID:IMSR_JAX:013755
Mus musculus with name B6.129S(C)-Batf3tm1Kmm/J from IMSR.
View all literature mentionsC57BL/6J (organism)
RRID:IMSR_JAX:000664
Mus musculus with name C57BL/6J from IMSR.
View all literature mentionsB6.129S2-Ifnar1tm1Agt/Mmjax (organism)
RRID:MMRRC_032045-JAX
Mus musculus with name B6.129S2-Ifnar1tm1Agt/Mmjax from MMRRC.
View all literature mentions
