Human Ascaris Infection is Associated with Higher Frequencies of IL-10 Producing B Cells

Overview

Journal PLoS Negl Trop Dis

Specialties Infectious Diseases
Tropical Medicine

Date 2024 Sep 23

PMID 39312581

Authors

Josefina Zakzuk

Juan F Lopez

Cezmi Akdis

Luis Caraballo

Mubeccel Akdis

Willem van de Veen

Affiliations

Soon will be listed here.

Abstract

Introduction: Ascaris lumbricoides has dual effects on the immune system of infected hosts. The IgE response to this parasite has been thoroughly studied, but little is known about cellular responses induced by infection. This study aims to explore the interplay between A. lumbricoides infection and B cell responses, especially B regulatory cells.

Methods: Participants from Santa Catalina, Bolívar, Colombia, a helminth-endemic town, were screened for soil-transmitted helminthiasis (STH) using stool examinations. Eighteen A. lumbricoides-infected and 11 non-infected subjects were selected. Blood samples were analyzed for Breg cells and related cytokines, and immunoglobulins specific to the A. lumbricoides excretory/secretory product, ABA-1.

Results: Infected subjects exhibited higher frequencies of Breg cells, especially those with a higher A. lumbricoides egg burden. Higher frequencies of different Breg subsets were observed in infected individuals, with CD25+CD71+CD73- B cells being notably increased in strongly infected individuals. Additionally, A. lumbricoides infection was associated with reduced levels of circulating ABA-1-specific IgG1 and IgE. IL-10+ B cell frequencies correlated inversely with ABA-1-specific IgE.

Conclusions: A. lumbricoides infection has a significant impact on the immune response, particularly on Breg cell populations and antibody responses. Our findings suggest that A. lumbricoides infection mediates a dose-dependent immunosuppressive response characterized by an increase in Breg cells and concomitant suppression of ABA-1-specific humoral responses.

References

Gary-Gouy H, Harriague J, Bismuth G, Platzer C, Schmitt C, Dalloul A . Human CD5 promotes B-cell survival through stimulation of autocrine IL-10 production. Blood. 2002; 100(13):4537-43. DOI: 10.1182/blood-2002-05-1525. View

Ruiter B, Knol E, van Neerven R, Garssen J, Bruijnzeel-Koomen C, Knulst A . Maintenance of tolerance to cow's milk in atopic individuals is characterized by high levels of specific immunoglobulin G4. Clin Exp Allergy. 2007; 37(7):1103-10. DOI: 10.1111/j.1365-2222.2007.02749.x. View

Abraham D, Kaliappan S, Walson J, Ajjampur S . Intervention strategies to reduce the burden of soil-transmitted helminths in India. Indian J Med Res. 2018; 147(6):533-544. PMC: 6118140. DOI: 10.4103/ijmr.IJMR_881_18. View

Piersiala K, Hjalmarsson E, Farrajota Neves da Silva P, Lagebro V, Kolev A, Starkhammar M . Regulatory B cells producing IL-10 are increased in human tumor draining lymph nodes. Int J Cancer. 2023; 153(4):854-866. DOI: 10.1002/ijc.34555. View

Pinot de Moira A, Fitzsimmons C, Jones F, Wilson S, Cahen P, Tukahebwa E . Suppression of basophil histamine release and other IgE-dependent responses in childhood Schistosoma mansoni/hookworm coinfection. J Infect Dis. 2014; 210(8):1198-206. PMC: 4176447. DOI: 10.1093/infdis/jiu234. View

Ummarino D . Rheumatoid arthritis: Defective IL-10-producing B cells. Nat Rev Rheumatol. 2017; 13(3):132. DOI: 10.1038/nrrheum.2017.10. View

Noh J, Lee J, Noh G, Bang S, Kim H, Choi W . Characterisation of allergen-specific responses of IL-10-producing regulatory B cells (Br1) in Cow Milk Allergy. Cell Immunol. 2010; 264(2):143-9. DOI: 10.1016/j.cellimm.2010.05.013. View

Cooper P, Chico M, Sandoval C, Espinel I, Guevara A, Levine M . Human infection with Ascaris lumbricoides is associated with suppression of the interleukin-2 response to recombinant cholera toxin B subunit following vaccination with the live oral cholera vaccine CVD 103-HgR. Infect Immun. 2001; 69(3):1574-80. PMC: 98058. DOI: 10.1128/IAI.69.3.1574-1580.2001. View

Veen W, Stanic B, Yaman G, Wawrzyniak M, Sollner S, Akdis D . IgG4 production is confined to human IL-10-producing regulatory B cells that suppress antigen-specific immune responses. J Allergy Clin Immunol. 2013; 131(4):1204-12. DOI: 10.1016/j.jaci.2013.01.014. View

10.

Sailliet N, Mai H, Dupuy A, Tilly G, Fourgeux C, Braud M . Human granzyme B regulatory B cells prevent effector CD4+CD25- T cell proliferation through a mechanism dependent from lymphotoxin alpha. Front Immunol. 2023; 14:1183714. PMC: 10425555. DOI: 10.3389/fimmu.2023.1183714. View

11.

Senaratna C, Perera P, Arulkumaran S, Abeysekara N, Piyumanthi P, Hamilton G . Association of helminth infestation with childhood asthma: a nested case-control study. Int J Infect Dis. 2023; 128:272-277. DOI: 10.1016/j.ijid.2023.01.004. View

12.

McSharry C, Xia Y, Holland C, Kennedy M . Natural immunity to Ascaris lumbricoides associated with immunoglobulin E antibody to ABA-1 allergen and inflammation indicators in children. Infect Immun. 1999; 67(2):484-9. PMC: 96345. DOI: 10.1128/IAI.67.2.484-489.1999. View

13.

Feng N, Zhang C, Cao W, Peng S, Jiang T, Liu Y . CD19CD24CD38 Regulatory B cells Involved in Hepatic Alveolar Hydatid Infection in Humans. Ann Clin Lab Sci. 2019; 49(3):338-343. View

14.

Takeuchi H, Khan A, Yunus M, Hasan M, Hawlader M, Takanashi S . Anti-Ascaris immunoglobulin E associated with bronchial hyper-reactivity in 9-year-old rural Bangladeshi children. Allergol Int. 2015; 65(2):141-146. DOI: 10.1016/j.alit.2015.07.002. View

15.

Kim D, Na H, Cho K, Lee K, Choi J, Kwok S . Sphingosylphosphorylcholine ameliorates experimental sjögren's syndrome by regulating salivary gland inflammation and hypofunction, and regulatory B cells. Immunol Lett. 2022; 248:62-69. DOI: 10.1016/j.imlet.2022.06.008. View

16.

Kalampokis I, Yoshizaki A, Tedder T . IL-10-producing regulatory B cells (B10 cells) in autoimmune disease. Arthritis Res Ther. 2013; 15 Suppl 1:S1. PMC: 3624502. DOI: 10.1186/ar3907. View

17.

Heeringa J, McKenzie C, Varese N, Hew M, Bakx A, Aui P . Induction of IgG and IgG B-cell memory following sublingual immunotherapy for ryegrass pollen allergy. Allergy. 2019; 75(5):1121-1132. PMC: 7317934. DOI: 10.1111/all.14073. View

18.

Chehayeb J, Robertson A, Martin R, Geary T . Proteomic analysis of adult Ascaris suum fluid compartments and secretory products. PLoS Negl Trop Dis. 2014; 8(6):e2939. PMC: 4046973. DOI: 10.1371/journal.pntd.0002939. View

19.

Wiest M, Upchurch K, Hasan M, Cardenas J, Lanier B, Millard M . Phenotypic and functional alterations of regulatory B cell subsets in adult allergic asthma patients. Clin Exp Allergy. 2019; 49(9):1214-1224. DOI: 10.1111/cea.13439. View

20.

van der Vlugt L, Zinsou J, Ozir-Fazalalikhan A, Kremsner P, Yazdanbakhsh M, Adegnika A . Interleukin 10 (IL-10)-producing CD1dhi regulatory B cells from Schistosoma haematobium-infected individuals induce IL-10-positive T cells and suppress effector T-cell cytokines. J Infect Dis. 2014; 210(8):1207-16. DOI: 10.1093/infdis/jiu257. View