Evaluation of Th1/Th2, regulatory cytokines and transcriptional factor FoxP3 in sheep immunized with a partially protective and non-protective vaccine and challenged with Fasciola hepatica.


Journal

Veterinary research
ISSN: 1297-9716
Titre abrégé: Vet Res
Pays: England
ID NLM: 9309551

Informations de publication

Date de publication:
24 Apr 2024
Historique:
received: 15 06 2023
accepted: 17 03 2024
medline: 25 4 2024
pubmed: 25 4 2024
entrez: 24 4 2024
Statut: epublish

Résumé

Gene expression for Th1/Th2 cytokines (IL-4 and IFN-ɣ), regulatory cytokines (TGF-β and IL-10) and the transcriptional factor FoxP3 was analyzed in the liver and hepatic lymph nodes (HLN) from sheep immunized with partially protective and non-protective vaccine candidates and challenged with Fasciola hepatica. FoxP3 T cells were also evaluated by immunohistochemistry (IHQ). The most remarkable difference between the partially protected vaccinated (V1) group and the non-protected vaccinated (V2) group was a more severe expansion of FoxP3 T cells recorded by IHQ in both the liver and HLN of the V2 group as compared to the V1 group, whereas no differences were found between the V2 group and the infected control (IC) group. Similar results were recorded for FoxP3 gene expression although significant differences among V1 and V2 groups were only significant in the HLN, while FoxP3 gene expression was very similar in the V2 and IC groups both in the liver and HLN. No significant differences for the remaining cytokines were recorded between the V1 and V2 groups, but in the liver the V2 group shows significant increases of IFN-ɣ and IL-10 as compared to the uninfected control (UC) group whereas the V1 group did not. The lower expansion of FoxP3 T cells and lower increase of IFN-ɣ and IL-10 in the partially protected vaccinated group may be related with lower hepatic lesions and fluke burdens recorded in this group as compared to the other two infected groups. The most relevant change in regulatory cytokine gene expression was the significant increase of TGF-β in the liver of IC, V1 and V2 groups as compared to the UC group, which could be related to hepatic lesions.

Identifiants

pubmed: 38658996
doi: 10.1186/s13567-024-01308-8
pii: 10.1186/s13567-024-01308-8
doi:

Substances chimiques

Forkhead Transcription Factors 0
Cytokines 0
Vaccines 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

53

Subventions

Organisme : Horizon 2020 Framework Programme
ID : H2020-635408-PARAGONE
Organisme : Ministerio de Ciencia, Innovación y Universidades
ID : AGL2015-67023-C2-1-R
Organisme : Consejería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía
ID : P18-RTJ-1956

Informations de copyright

© 2024. The Author(s).

Références

Mehmood K, Zhang H, Sabir AJ, Abbas RZ, Ijaz M, Durrani AZ, Saleem MH, Ur Rehman M, Iqbal MK, Wang Y, Ahmad HI, Abbas T, Hussain R, Ghori MT, Ali S, Khan AU, Li J (2017) A review on epidemiology, global prevalence and economical losses of fasciolosis in ruminants. Microb Pathog 109:253–262
doi: 10.1016/j.micpath.2017.06.006 pubmed: 28602837
Mas-Coma S, Bargues MD, Valero MA (2018) Human fascioliasis infection sources, their diversity, incidence factor, analytical methods and prevention measures. Parasitology 11:1665–1699
doi: 10.1017/S0031182018000914
Fairweather I, Brennan GP, Hanna REB, Robinson MW, Skuce PJ (2020) Drug resistance in liver flukes. Int J Parasitol Drug Drug Resist 12:39-59
doi: 10.1016/j.ijpddr.2019.11.003
Spithill TW, Toet H, Rathinasamy V, Zerna G, Swan J, Cameron T, Smooker PM, Piedrafita DM, Dempster R, Bebdoe T (2022) Vaccines for fasciola: new thinking for and old problem. In: Dalton JP (ed) Fasciolosis, 2
Molina-Hernández V, Mulcahy G, Pérez J, Martínez-Moreno Á, Donnelly S, O’Neill SM, Dalton JP, Cwiklinski K (2015) Fasciola hepatica vaccine: we may not be there yet but we’re on the right road. Vet Parasitol 208:101–111
doi: 10.1016/j.vetpar.2015.01.004 pubmed: 25657086 pmcid: 4366043
Pacheco IL, Abril N, Zafra R, Molina-Hernández V, Morales-Prieto N, Bautista MJ, Ruiz-Campillo MT, Pérez-Caballero R, Martínez-Moreno A, Pérez J (2018) Fasciola hepatica induces Foxp3 T cell, proinflammatory and regulatory cytokine overexpression in liver from infected sheep during early stages of infection. Vet Res 49:56
doi: 10.1186/s13567-018-0550-x pubmed: 29970179 pmcid: 6029414
McNeilly TN, Rocchi M, Bartley Y, Brown JK, Frew D, Longhi C, McLean L, McIntyre J, Nisbet AJ, Wattegedera S, Huntley JF, Matthews JB (2013) Suppression of ovine lymphocyte activation by Teladorsagia circumcincta larval excretory–secretory products. Vet Res 44:70
doi: 10.1186/1297-9716-44-70 pubmed: 23964850 pmcid: 3848371
Escamilla A, Zafra R, Pérez J, McNeilly TN, Pacheco IL, Buffoni L, Martínez-Moreno FJ, Molina-Hernández V, Martínez-Moreno A (2016) Distribution of Foxp3+ T cells in the liver and hepatic lymph nodes of goats and sheep experimentally infected with Fasciola hepatica. Vet Parasitol 230:14–19
doi: 10.1016/j.vetpar.2016.10.020 pubmed: 27884436
Pacheco IL, Abril N, Morales-Prieto N, Bautista MJ, Zafra R, Escamilla A, Ruiz MT, Martínez-Moreno A, Pérez J (2017) Th1/Th2 balance in the liver and hepatic lymph nodes of vaccinated and unvaccinated sheep during acute stages of infection with Fasciola hepatica. Vet Parasitol 238:61–65
doi: 10.1016/j.vetpar.2017.03.022 pubmed: 28385539
Ingale SL, Singh P, Raina OK, Mehra UR, Verma AK, Gupta SC, Mulik SV (2008) Interferon–gamma and interleukin–4 expression during Fasciola gigantica primary infection in crossbred bovine calves as determined by real–time PCR. Vet Parasitol 152:158–161
doi: 10.1016/j.vetpar.2007.11.023 pubmed: 18201826
Graham-Brown J, Hartley C, Clough H, Kadioglu A, Baylis M, Williams DJL (2017) Dairy heifers naturally exposed to Fasciola hepatica develop a type 2 immune response and concomitant suppression of leukocyte proliferation. Infect Immun 86:e00607-17
pubmed: 28993458 pmcid: 5736823
Corrêa F, Hidalgo C, Stoore C, Jiménez M, Hernández M, Paredes R (2020) Cattle co-infection of Echinococcus granulosus and Fasciola hepatica results in a different systemic cytokine profile than single parasite infection. PLoS One 15:e0238909
doi: 10.1371/journal.pone.0238909 pubmed: 32915902 pmcid: 7485845
Chung JY, Bae YA, Yun DH, Yang HJ, Kong Y (2012) Experimental murine fascioliasis derives early immune suppression with increased levels of TGFβ and IL–4. Korean J Parasitol 50:301–308
doi: 10.3347/kjp.2012.50.4.301 pubmed: 23230327 pmcid: 3514421
Valero MA, Perez-Crespo I, Chillón-Marinas C, Khoubbane M, Quesada C, Reguera-Gomez M, Mas-Coma S, Fresno M, Gironès N (2017) Fasciola hepatica reinfection potentiates a mixed Th1/Th2/Th17/Treg response and correlates with the clinical phenotypes of anemia. PLoS One 12:e0173456
doi: 10.1371/journal.pone.0173456 pubmed: 28362822 pmcid: 5376296
Golden O, Flynn RJ, Rea C, Sekiya M, Donnelly SM, Stack C, Dalton JP, Mulcahy G (2010) Protection of cattle against a natural infection of Fasciola hepatica by vaccination with recombinant cathepsin L1 (rFhCL1). Vaccine 28:5551–5557
doi: 10.1016/j.vaccine.2010.06.039 pubmed: 20600503
Maggioli G, Acosta D, Silveira F, Rossi S, Giacaman S, Basika T, Gayo V, Rosadilla D, Roche L, Tort J, Carmona C (2011) The recombinant gut-associated M17 leucine aminopeptidase in combination with different adjuvants confers a high level of protection against Fasciola hepatica infection in sheep. Vaccine 29:9057–9063
doi: 10.1016/j.vaccine.2011.09.020 pubmed: 21939713
Zafra R, Buffoni L, Pérez-Caballero R, Molina-Hernández V, Ruiz-Campillo MT, Pérez J, Martínez-Moreno Á, Martínez Moreno FJ (2021) Efficacy of a multivalent vaccine against Fasciola hepatica infection in sheep. Vet Res 52:13
doi: 10.1186/s13567-021-00895-0 pubmed: 33509286 pmcid: 7841919
Villa-Mancera A, Olivares-Pérez J, Olmedo-Juárez A, Reynoso-Palomar A (2021) Phage display-based vaccine with cathepsin L and excretory-secretory products mimotopes of Fasciola hepatica induces protective cellular and humoral immune responses in sheep. Vet Parasitol 289:109340
doi: 10.1016/j.vetpar.2020.109340 pubmed: 33373968
Molina-Hernández V, Ruiz-Campillo MT, Martínez-Moreno FJ, Buffoni L, Martínez-Moreno Á, Zafra R, Bautista MJ, Escamilla A, Pérez-Caballero R, Pérez J (2021) A partially protective vaccine for Fasciola hepatica induced degeneration of adult flukes associated to a severe granulomatous reaction in sheep. Animals 11:2869
doi: 10.3390/ani11102869 pubmed: 34679889 pmcid: 8532621
Ruiz-Campillo MT, Barrero-Torres DM, Abril N, Pérez J, Zafra R, Buffoni L, Martínez-Moreno Á, Martínez-Moreno FJ, Molina-Hernández V (2023) Fasciola hepatica primoinfections and reinfections in sheep drive distinct Th1/Th2/Treg immune responses in liver and hepatic lymph node at early and late stages. Vet Res 54:2
doi: 10.1186/s13567-022-01129-7 pubmed: 36627694 pmcid: 9832625
Schroeder A, Mueller O, Stocker S, Salowsky R, Leiber M, Gassman M, Lightfoot S, Menzel W, Granzow M, Ragg T (2006) The RIN: an RNA integrity number for assigning integrity values to RNA measurements. BMC Mol Biol 7:3
doi: 10.1186/1471-2199-7-3 pubmed: 16448564 pmcid: 1413964
Pacheco IL, Abril N, Zafra R, Morales-Prieto N, Molina-Hernández V, Ruiz MT, Pérez-Caballero R, Martínez-Moreno A, Pérez J (2019) Identification of reference genes for real-time PCR cytokine gene expression studies in sheep experimentally infected with Fasciola hepatica. Sci Rep 9:1485
doi: 10.1038/s41598-018-37672-7 pubmed: 30728395 pmcid: 6365638
Prieto-Alamo MJ, Cabrera-Luque JM, Pueyo C (2003) Absolute quantitation of normal and ROS-induced patterns of gene expression: an in vivo real-time PCR study in mice. Gene Expr 11:23–34
doi: 10.3727/000000003783992315 pubmed: 12691523
Jurado J, Fuentes-Almagro CA, Prieto-Alamo MJ, Pueyo C (2007) Alternative splicing of c-fos pre-mRNA: contribution of the rates of synthesis and degradation to the copy number of each transcript isoform and detection of a truncated c-Fos immunoreactive species. BMC Mol Biol 8:83
doi: 10.1186/1471-2199-8-83 pubmed: 17888145 pmcid: 2098773
Sachdev D, Gough KC, Flynn RJ (2017) The chronic stages of bovine Fasciola hepatica are dominated by CD4 T-cell exhaustion. Front Immunol 8:1002
doi: 10.3389/fimmu.2017.01002 pubmed: 28871261 pmcid: 5566560
Shi W, Wei ZY, Elsheikha HM, Zhang FK, Sheng ZA, Lu KJ, Wang DY, Huang WY, Zhu XQ (2017) Dynamic expression of cytokine and transcription factor genes during experimental Fasciola gigantica infection in buffaloes. Parasit Vector 10:602
doi: 10.1186/s13071-017-2538-1
Mendes EA, Mendes TA, dos Santos SL, Menezes-Souza D, Bartholomeu DC, Martins IV, Silva LM, dos Santos LW (2013) Expression of IL-4, IL-10 and IFN-γ in the liver tissue of cattle that are naturally infected with Fasciola hepatica. Vet Parasitol 195:177–182
doi: 10.1016/j.vetpar.2013.03.035 pubmed: 23648284
Silvane L, Celias DP, Romagnoli PA, Maletto BA, Sanchez Vallecillo MF, Chiapello LS, Palma SD, Allemandi DA, Sanabria REF, Pruzzo CI, Motrán CC, Cervi L (2020) A vaccine based on Kunitz-type molecule confers protection against Fasciola hepatica challenge by inducing IFN-γ and antibody immune responses through IL-17A production. Front Immunol 11:2087
doi: 10.3389/fimmu.2020.02087 pubmed: 33193292 pmcid: 7641617
Fu Y, Chryssafidis AL, Browne JA, O’Sullivan J, McGettigan PA, Mulcahy G (2016) Transcriptomic study on ovine immune responses to Fasciola hepatica infection. PLoS Negl Trop Dis 10:e0005015
doi: 10.1371/journal.pntd.0005015 pubmed: 27661612 pmcid: 5035020
Waldvogel AS, Lepage MF, Zakher A, Reichel MP, Eicher R, Heussler VT (2004) Expression of interleukin 4, interleukin 4 splice variants and interferon gamma mRNA in calves experimentally infected with Fasciola hepatica. Vet Immunol Immunopathol 97:53–63
doi: 10.1016/j.vetimm.2003.08.002 pubmed: 14700537
Naranjo-Lucena A, Correia CN, Molina-Hernández V, Martínez-Moreno Á, Browne JA, Pérez J, MacHugh DE, Mulcahy G (2021) Transcriptomic analysis of ovine hepatic lymph node following Fasciola hepatica infection—inhibition of NK cell and IgE-mediated signaling. Front Immunol 12:687579
doi: 10.3389/fimmu.2021.687579 pubmed: 34122452 pmcid: 8194261
Flynn RJ, Mulcahy G (2008) The roles of IL-10 and TGF-beta in controlling IL-4 and IFN-gamma production during experimental Fasciola hepatica infection. Int J Parasitol 38:1673–1680
doi: 10.1016/j.ijpara.2008.05.008 pubmed: 18597757
Cutroneo KR (2007) TGF-β induced fibrosis and SMAD signaling: oligo decoys as natural therapeutics for inhibition of tissue fibrosis and scarring. Wound Rep Reg 15:54–60
doi: 10.1111/j.1524-475X.2007.00226.x
Pérez J, Ortega J, Moreno T, Morrondo P, López-Sández C, Martínez-Moreno A (2002) Pathological and immunohistochemical study of the liver and hepatic lymph nodes of sheep chronically reinfected with Fasciola hepatica, with or without triclabendazole treatment. J Comp Pathol 127:30–36
doi: 10.1053/jcpa.2002.0561 pubmed: 12354543
Niedziela DA, Naranjo-Lucena A, Molina-Hernández V, Browne JA, Martínez-Moreno Á, Pérez J, MacHugh DE, Mulcahy G (2021) Timing of transcriptomic peripheral blood mononuclear cell responses of sheep to Fasciola hepatica infection differs from those of cattle, reflecting different disease phenotypes. Front Immunol 12:729217
doi: 10.3389/fimmu.2021.729217 pubmed: 34616397 pmcid: 8488161
Sheng ZA, Li J, Wang DY, Kang YQ, Wei ZY, Zhang FK, Zhu XQ, Luo HL, Huang WY (2019) Th2-related cytokines are associated with Fasciola gigantica infection and evasion in the natural host, swamp buffalo. Vet Parasitol 268:73–80
doi: 10.1016/j.vetpar.2019.03.001 pubmed: 30981309

Auteurs

María Teresa Ruiz-Campillo (MT)

Departamento de Anatomía y Anatomía Patológica Comparadas y Toxicología, Facultad de Veterinaria, UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Edificio de Sanidad Animal, Campus de Rabanales, Ctra. Madrid-Cádiz Km 396, 14014, Córdoba, Spain.

Isabel Lourdes Pacheco (IL)

Departamento de Anatomía y Anatomía Patológica Comparadas y Toxicología, Facultad de Veterinaria, UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Edificio de Sanidad Animal, Campus de Rabanales, Ctra. Madrid-Cádiz Km 396, 14014, Córdoba, Spain.

Nieves Abril (N)

Departamento de Bioquímica y Biología Molecular, Universidad de Córdoba, Edificio Severo Ochoa, Campus de Rabanales, Ctra. Madrid-Cádiz Km 396, 14014, Córdoba, Spain.

María José Bautista (MJ)

Departamento de Anatomía y Anatomía Patológica Comparadas y Toxicología, Facultad de Veterinaria, UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Edificio de Sanidad Animal, Campus de Rabanales, Ctra. Madrid-Cádiz Km 396, 14014, Córdoba, Spain.

Álvaro Martínez-Moreno (Á)

Departamento de Sanidad Animal (Parasitología), Facultad de Veterinaria, UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Edificio de Sanidad Animal, Campus de Rabanales, Ctra. Madrid-Cádiz Km 396, 14014, Córdoba, Spain.

Francisco Javier Martínez-Moreno (FJ)

Departamento de Sanidad Animal (Parasitología), Facultad de Veterinaria, UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Edificio de Sanidad Animal, Campus de Rabanales, Ctra. Madrid-Cádiz Km 396, 14014, Córdoba, Spain.

Leandro Buffoni (L)

Departamento de Sanidad Animal (Parasitología), Facultad de Veterinaria, UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Edificio de Sanidad Animal, Campus de Rabanales, Ctra. Madrid-Cádiz Km 396, 14014, Córdoba, Spain.

José Pérez (J)

Departamento de Anatomía y Anatomía Patológica Comparadas y Toxicología, Facultad de Veterinaria, UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Edificio de Sanidad Animal, Campus de Rabanales, Ctra. Madrid-Cádiz Km 396, 14014, Córdoba, Spain.

Verónica Molina-Hernández (V)

Departamento de Anatomía y Anatomía Patológica Comparadas y Toxicología, Facultad de Veterinaria, UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Edificio de Sanidad Animal, Campus de Rabanales, Ctra. Madrid-Cádiz Km 396, 14014, Córdoba, Spain. vmolina@uco.es.

Rafael Zafra (R)

Departamento de Sanidad Animal (Parasitología), Facultad de Veterinaria, UIC Zoonosis y Enfermedades Emergentes ENZOEM, Universidad de Córdoba, Edificio de Sanidad Animal, Campus de Rabanales, Ctra. Madrid-Cádiz Km 396, 14014, Córdoba, Spain.

Articles similaires

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male
Humans Meals Time Factors Female Adult

Classifications MeSH