Ascaris suum infection in juvenile pigs elicits a local Th2 response in a setting of ongoing Th1 expansion

被引:5
作者
Oser, Larissa [1 ]
Midha, Ankur [1 ]
Schlosser-Brandenburg, Josephine [1 ]
Rausch, Sebastian [1 ]
Mugo, Robert M. [1 ]
Kundik, Arkadi [1 ]
Elizalde-Velazquez, Luis E. [1 ]
Adjah, Joshua [1 ]
Musimbi, Zaneta D. [1 ]
Klopfleisch, Robert [2 ]
Helm, Christina S. [3 ]
von Samson-Himmelstjerna, Georg [3 ]
Hartmann, Susanne [1 ]
Ebner, Friederike [1 ,4 ]
机构
[1] Free Univ Berlin, Inst Immunol, Ctr Infect Med, Dept Vet Med, Berlin, Germany
[2] Free Univ Berlin, Inst Vet Pathol, Dept Vet Med, Berlin, Germany
[3] Free Univ Berlin, Inst Parasitol & Trop Vet Med, Dept Vet Med, Berlin, Germany
[4] Tech Univ Munich, Sch Life Sci, Infect Pathogenesis, Freising Weihenstephan, Germany
关键词
pig; soil-transmitted helminth; Ascaris suum; antigen-specific; adaptive immunity; infection; protection; Th1/Th2; REGULATORY T-CELLS; PROTECTIVE IMMUNITY; TRICHURIS-MURIS; PARASITIC HELMINTHS; TOXOPLASMA-GONDII; TISSUE MIGRATION; HEPATIC-LESIONS; FATTENING PIGS; CYTOKINE; LUMBRICOIDES;
D O I
10.3389/fimmu.2024.1396446
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Ascaris spp. undergo extensive migration within the body before establishing patent infections in the small intestinal tract of humans and pigs. However, whether larval migration is critical for inducing efficient type 2 responses remains poorly understood. Therefore, we investigated systemic versus local adaptive immune responses along the hepato-tracheal migration of Ascaris suum during primary, single infections in conventionally raised pigs. Neither the initial invasion of gut tissue nor migration through the liver resulted in discernable Th2 cell responses. In contrast, lung-stage larvae elicited a Th2-biased pulmonary response, which declined after the larvae had left the lungs. In the small intestine, we observed an accumulation of Th2 cells upon the arrival of fourth-stage larvae (L4) to the small intestinal lumen. In parallel, we noticed robust and increasing Th1 responses in circulation, migration-affected organs, and draining lymph nodes. Phenotypic analysis of CD4+ T cells specifically recognizing A. suum antigens in the circulation and lung tissue of infected pigs confirmed that the majority of Ascaris-specific T cells produced IL-4 (Th2) and, to a much lesser extent, IL-4/IFN-g (Th2/1 hybrids) or IFN-g alone (Th1). These data demonstrate that lung-stage but not the early liver-stage larvae lead to a locally restricted Th2 response. Significant Th2 cell accumulation in the small intestine occurs only when L4 complete the body migration. In addition, Th2 immunity seems to be hampered by the concurrent, nonspecific Th1 bias in growing pigs. Together, the late onset of Th2 immunity at the site of infection and the Th1-biased systemic immunity likely enable the establishment of intestinal infections by sufficiently large L4 stages and pre-adult worms, some of which resist expulsion mechanisms.
引用
收藏
页数:16
相关论文
共 94 条
[1]   Toxoplasma Co-infection Prevents Th2 Differentiation and Leads to a Helminth-Specific Th1 Response [J].
Ahmed, Norus ;
French, Timothy ;
Rausch, Sebastian ;
Kuehl, Anja ;
Hemminger, Katrin ;
Dunay, Ildiko R. ;
Steinfelder, Svenja ;
Hartmann, Susanne .
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 2017, 7
[2]   A comparison of Mini-FLOTAC and McMaster techniques in detecting gastrointestinal parasites in West Africa Dwarf sheep and goats and crossbreed rabbits [J].
Alowanou, Georcelin G. ;
Adenile, Adam D. ;
Akouedegni, Guenole C. ;
Bossou, Arsene C. ;
Zinsou, Frejus T. ;
Akakpo, Gilles-Christ A. ;
Kifouly, Habirou A. ;
Rinaldi, Laura ;
von Samson-Himmelstjerma, Georg ;
Cringoli, Giuseppe ;
Hounzangbe-Adote, Sylvie .
JOURNAL OF APPLIED ANIMAL RESEARCH, 2021, 49 (01) :30-38
[3]   Protective immune mechanisms in helminth infection [J].
Anthony, Robert M. ;
Rutitzky, Laura I. ;
Urban, Joseph F., Jr. ;
Stadecker, Miguel J. ;
Gause, William C. .
NATURE REVIEWS IMMUNOLOGY, 2007, 7 (12) :975-987
[4]   Phenotype and Function of Human T Lymphocyte Subsets: Consensus and Issues [J].
Appay, Victor ;
van Lier, Rene A. W. ;
Sallusto, Federica ;
Roederer, Mario .
CYTOMETRY PART A, 2008, 73A (11) :975-983
[5]   EPIDEMIOLOGY OF HELMINTH DISEASE IN FARM-ANIMALS [J].
ARMOUR, J .
VETERINARY PARASITOLOGY, 1980, 6 (1-3) :7-46
[6]  
Bancroft JD., 1996, Theory and practice of histological techniques, DOI DOI 10.1002/(SICI)1096-9896(199710)183:2<243::AID-PATH770>3.0.CO
[7]  
2-F
[8]   Strong effects of lab-to-field environmental transitions on the bacterial intestinal microbiota of Mus musculus are modulated by Trichuris muris infection [J].
Bar, Julian ;
Leung, Jacqueline M. ;
Hansen, Christina ;
Loke, P'ng ;
Hall, Alex R. ;
Conour, Laura ;
Graham, Andrea L. .
FEMS MICROBIOLOGY ECOLOGY, 2020, 96 (10)
[9]  
Betts CJ, 2000, PARASITOLOGY, V121, P631
[10]   Concomitant Infection of S. mansoni and H. pylori Promotes Promiscuity of Antigen-Experienced Cells and Primes the Liver for a Lower Fibrotic Response [J].
Bhattacharjee, Sonakshi ;
Mejias-Luque, Raquel ;
Loffredo-Verde, Eva ;
Toska, Albulena ;
Flossdorf, Michael ;
Gerhard, Markus ;
da Costa, Clarissa Prazeres .
CELL REPORTS, 2019, 28 (01) :231-+