Staphylococcus aureus Promotes Smed-PGRP-2/Smed-setd8-1 Methyltransferase Signalling in Planarian Neoblasts to Sensitize Anti-bacterial Gene Responses During Re-infection

Cedric Torre (1) , Prasad Abnave (1) , Landry Laure Tsoumtsa (1) , Giovanna Mottola (2, 3) , Catherine Lepolard (1) , Virginie Trouplin (4) , Gregory Gimenez (5) , Julie Desrousseaux (6) , Stephanie Gempp (6) , Anthony Levasseur (1) , Laetitia Padovani (7) , Emmanuel Lemichez (8) , Eric Ghigo (1)

1 URMITE - Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes
2 AMU - Aix Marseille Université
3 DS-ACI / UMR MD2 - Dysoxie, suractivité : aspects cellulaires et intégratifs thérapeutiques
4 INT - Institut de Neurosciences de la Timone
5 CIML - Centre d'Immunologie de Marseille - Luminy
6 TIMONE - Hôpital de la Timone [CHU - APHM]
7 CRO2 - Centre de Recherches en Oncologie biologique et Oncopharmacologie
8 C3M - Centre méditerranéen de médecine moléculaire

Little is known about how organisms exposed to recurrent infections adapt their innate immune responses. Here, we report that planarians display a form of instructed immunity to primo-infection by Staphylococcus aureus that consists of a transient state of heightened resistance to re-infection that persists for approximately 30 days after primo-infection. We established the involvement of stem cell-like neoblasts in this instructed immunity using the complementary approaches of RNA-interference-mediated cell depletion and tissue grafting-mediated gain of function. Mechanistically, primo-infection leads to expression of the peptidoglycan receptor Smed-PGRP-2, which in turn promotes Smed-setd8-1 histone methyltransferase expression and increases levels of lysine meth-ylation in neoblasts. Depletion of neoblasts did not affect S. aureus clearance in primo-infection but, in re-infection , abrogated the heightened elimination of bacteria and reduced Smed-PGRP-2 and Smed-setd8-1 expression. Smed-PGRP-2 and Smed-setd8-1 sensitize animals to heightened expression of Smed-p38 MAPK and Smed-morn2, which are downstream components of anti-bacterial responses. Our study reveals a central role of neoblasts in innate immunity against S. aureus to establish a resistance state facilitating Smed-sted8-1-dependent expression of anti-bacterial genes during re-infection.

Mots clés: S aureus; Planarians; Neoblasts; PGRP-2; sted8-1; Instructed immunity; Stem cells

Domaines: Immunité innée

Cedric Torre, Prasad Abnave, Landry Laure Tsoumtsa, Giovanna Mottola, Catherine Lepolard, et al.. Staphylococcus aureus Promotes Smed-PGRP-2/Smed-setd8-1 Methyltransferase Signalling in Planarian Neoblasts to Sensitize Anti-bacterial Gene Responses During Re-infection. EBioMedicine, 2017, 20, pp.150-160. ⟨10.1016/j.ebiom.2017.04.031⟩. ⟨hal-01796117v2⟩