Title :

Cytotoxic innate intraepithelial lymphocytes control early stages of Cryptosporidium infection

Author(s) :

Hariss, Fatima [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Delbeke, Marie [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Guyot, Karine [Auteur]
Institut Pasteur de Lille
Zarnitzky, Pauline [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Ezzedine, Mohamad [Auteur]
Certad, Gabriela [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Groupement des Hôpitaux de l'Institut Catholique de Lille [GHICL]
Meresse, Bertrand [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]

Journal title :

Frontiers in immunology

Volume number :

14

Publisher :

Frontiers

Publication date :

2023-09-06

ISSN :

1664-3224

English keyword(s) :

gut innate intraepithelial lymphocytes cryptosporidium organoids cytotoxicity
gut
innate intraepithelial lymphocytes
cryptosporidium
organoids
cytotoxicity

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Background: Intraepithelial lymphocytes (IELs) are the first immune cells to contact and fight intestinal pathogens such as Cryptosporidium, a widespread parasite which infects the gut epithelium. IFN-g producing CD4 + T ...
Show more >Background: Intraepithelial lymphocytes (IELs) are the first immune cells to contact and fight intestinal pathogens such as Cryptosporidium, a widespread parasite which infects the gut epithelium. IFN-g producing CD4 + T IELs provide an efficient and a long-term protection against cryptosporidiosis while intraepithelial type 1 innate lymphoid cells limits pathogen spreading during early stages of infection in immunodeficient individuals. Yet, the role of T-cell like innate IELs, the most frequent subset of innate lymphocytes in the gut, remains unknown. Methods: To better define functions of innate IELs in cryptosporidiosis, we developed a co-culture model with innate IELs isolated from Rag2-/-mice and 3D intestinal organoids infected with C. parvum using microinjection. Results: Thanks to this original model, we demonstrated that innate IELs control parasite proliferation. We further showed that although innate IELs secrete IFN-g in response to C. parvum, the cytokine was not sufficient to inhibit parasite proliferation at early stages of the infection. The rapid protective effect of innate IELs was in fact mediated by a cytotoxic, granzyme-dependent mechanism. Moreover, transcriptomic analysis of the Cryptosporidium-infected organoids revealed that epithelial cells down regulated Serpinb9b, a granzyme inhibitor, which may increase their sensitivity to cytolytic attack by innate IELs. Conclusion: Based on these data we conclude that innate IELs, most likely T-celllike innate IELs, provide a rapid protection against C. parvum infection through a perforin/granzymes-dependent mechanism. C. parvum infection. The infection may also increase the sensitivity of intestinal epithelial cells to the innate IELmediated cytotoxic attack by decreasing the expression of Serpin genes.Show less >

Language :

Anglais

Popular science :

Non

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Submission date :

2024-02-24T04:28:46Z
2024-03-04T15:18:00Z