Gut symbiotic microbes imprint intestinal immune cells with the innate receptor SLAMF4 which contributes to gut immune protection against enteric pathogens.
Interactions between host immune cells and gut microbiota are crucial for the integrity and function of the intestine. How these interactions regulate immune cell responses in the intestine remains a major gap in the field.



We have identified the signalling lymphocyte activation molecule family member 4 (SLAMF4) as an immunomodulator of the intestinal immunity. The aim is to determine how SLAMF4 is acquired in the gut and what its contribution to intestinal immunity is.



Expression of SLAMF4 was assessed in mice and humans. The mechanism of induction was studied using GFPtgbone marrow chimaera mice, lymphotoxin α and TNLG8A-deficient mice, as well as gnotobiotic mice. Role in immune protection was revealed using oral infection withListeria monocytogenesandCytobacter rodentium.



SLAMF4 is a selective marker of intestinal immune cells of mice and humans. SLAMF4 induction occurs directly in the intestinal mucosa without the involvement of the gut-associated lymphoid tissue. Gut bacterial products, particularly those of gut anaerobes, and gut-resident antigen-presenting cell (APC)TNLG8Aare key contributors of SLAMF4 induction in the intestine. Importantly, lack of SLAMF4 expression leads the increased susceptibility of mice to infection by oral pathogens culminating in their premature death.



SLAMF4 is a marker of intestinal immune cells which contributes to the protection against enteric pathogens and whose expression is dependent on the presence of the gut microbiota. This discovery provides a possible mechanism for answering the long-standing question of how the intertwining of the host and gut microbial biology regulates immune cell responses in the gut.
The Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey, USA.
Allison
A
Cabinian
The Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey, USA.
Daniel
D
Sinsimer
The Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey, USA.
May
M
Tang
Department of Microbiology and Immunology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
Youngsoon
Y
Jang
Department of Microbiology and Immunology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
Bongkum
B
Choi
Department of Microbiology and Immunology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
Yasmina
Y
Laouar
The Child Health Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey, USA.
Amale
A
Laouar
D000818:Animals; D005434:Flow Cytometry; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D005856:Germ-Free Life; D006801:Humans; D018928:Immunity, Mucosal / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D000071176:Signaling Lymphocytic Activation Molecule Family / Q000378:metabolism*; D013559:Symbiosis
C084093:CD244 protein, human; C490007:Cd244a protein, mouse; D000071176:Signaling Lymphocytic Activation Molecule Family
ANTIBIOTICS; ENTERIC INFECTIONS; GASTROINTESTINAL IMMUNE RESPONSE; INTESTINAL BACTERIA; MUCOSAL IMMUNITY