Microbial ecology perturbation in human IgA deficiency

Jehane Fadlallah (1) , Hela El Kafsi (1) , Delphine Sterlin (1, 2) , Catherine Juste (3) , Christophe Parizot (2) , Karim Dorgham (1) , Gaëlle Autaa (1) , Doriane Gouas (1) , Mathieu Almeida (4) , Patricia Lepage (3) , Nicolas Pons (5) , Emmanuelle Le Chatelier (5) , Florence Levenez (5) , Sean Kennedy (5) , Nathalie N. Galleron (5) , Jean-Paul Pais de Barros (6, 7) , Marion Malphettes (8) , Lionel Galicier (8) , David Boutboul (8, 9) , Alexis Mathian (10, 11) , Makoto Miyara (1, 2) , Eric Oksenhendler (8, 12) , Zahir Amoura (10, 11, 1) , Joel Dore (3, 5) , Claire Fieschi (8, 9) , S. Dusko Ehrlich (13, 5) , Martin Larsen (1, 2) , Guy Gorochov (2, 1)

1 CIMI - Centre d'Immunologie et des Maladies Infectieuses
2 Service d'Immunologie [CHU Pitié-Salpétrière]
3 MICALIS - MICrobiologie de l'ALImentation au Service de la Santé
4 University of Maryland [College Park]
5 MetaGenoPolis
6 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
7 LabEx LipSTIC - Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer
8 AP-HP - Hopital Saint-Louis [AP-HP]
9 Différenciation et progression tumorale des lymphocytes
10 Service de médecine interne [CHU Pitié-Salpétrière]
11 Institut E3M [CHU Pitié-Salpêtrière]
12 URP_3518 - Recherche clinique appliquée à l'hématologie
13 King‘s College London

Paradoxically, loss of immunoglobulin A (IgA), one of the most abundant antibodies, does not irrevocably lead to severe infections in humans but rather is associated with relatively mild respiratory infections, atopy, and autoimmunity. IgA might therefore also play covert roles, not uniquely associated with control of pathogens. We show that human IgA deficiency is not associated with massive quantitative perturbations of gut microbial ecology. Metagenomic analysis highlights an expected pathobiont expansion but a less expected depletion in some typically beneficial symbionts. Gut colonization by species usually present in the oropharynx is also reminiscent of spatial microbiota disorganization. IgM only partially rescues IgA deficiency because not all typical IgA targets are efficiently bound by IgM in the intestinal lumen. Together, IgA appears to play a nonredundant role at the forefront of the immune/microbial interface, away from the intestinal barrier, ranging from pathobiont control and regulation of systemic inflammation to preservation of commensal diversity and community networks.

Mots clés: Colonization; Human gut microbiome; Memory b-cells; Immunoglobulin-a; T-cells; Secretory antibodies; Bacteria; Homeostasis; Innate; Lipopolysaccharide

Domaines: Sciences du Vivant [q-bio]; Biologie cellulaire

Jehane Fadlallah, Hela El Kafsi, Delphine Sterlin, Catherine Juste, Christophe Parizot, et al.. Microbial ecology perturbation in human IgA deficiency. Science Translational Medicine, 2018, 10 (439), pp.eaan1217. ⟨10.1126/scitranslmed.aan1217⟩. ⟨hal-01997107⟩