Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria.
The mammalian intestinal tract is colonized by trillions of beneficial commensal bacteria that are anatomically restricted to specific niches. However, the mechanisms that regulate anatomical containment remain unclear. Here, we show that interleukin-22 (IL-22)-producing innate lymphoid cells (ILCs) are present in intestinal tissues of healthy mammals. Depletion of ILCs resulted in peripheral dissemination of commensal bacteria and systemic inflammation, which was prevented by administration of IL-22. Disseminating bacteria were identified as Alcaligenes species originating from host lymphoid tissues. Alcaligenes was sufficient to promote systemic inflammation after ILC depletion in mice, and Alcaligenes-specific systemic immune responses were associated with Crohn's disease and progressive hepatitis C virus infection in patients. Collectively, these data indicate that ILCs regulate selective containment of lymphoid-resident bacteria to prevent systemic inflammation associated with chronic diseases.
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Gregory F
GF
Sonnenberg
Laurel A
LA
Monticelli
Theresa
T
Alenghat
Thomas C
TC
Fung
Natalie A
NA
Hutnick
Jun
J
Kunisawa
Naoko
N
Shibata
Stephanie
S
Grunberg
Rohini
R
Sinha
Adam M
AM
Zahm
Mélanie R
MR
Tardif
Taheri
T
Sathaliyawala
Masaru
M
Kubota
Donna L
DL
Farber
Ronald G
RG
Collman
Abraham
A
Shaked
Lynette A
LA
Fouser
David B
DB
Weiner
Philippe A
PA
Tessier
Joshua R
JR
Friedman
Hiroshi
H
Kiyono
Frederic D
FD
Bushman
Kyong-Mi
KM
Chang
David
D
Artis
D000328:Adult; D000421:Alcaligenes / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D000818:Animals; D018988:Bacterial Translocation; D003424:Crohn Disease / Q000276:immunology / Q000382:microbiology; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation; D007378:Interleukins / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology*; D007422:Intestines / Q000276:immunology* / Q000382:microbiology; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D008099:Liver / Q000382:microbiology; D008198:Lymph Nodes / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology* / Q000382:microbiology*; D008253:Macaca mulatta; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D013154:Spleen / Q000382:microbiology; D055815:Young Adult; D000097043:Interleukin-22
D007378:Interleukins; D039841:Leukocyte L1 Antigen Complex; D000097043:Interleukin-22