Hostname: page-component-848d4c4894-p2v8j Total loading time: 0.001 Render date: 2024-06-03T08:55:58.231Z Has data issue: false hasContentIssue false

Tissue eosinophilia correlates with mice susceptibility, granuloma formation and damage during Toxocara canis infection

Published online by Cambridge University Press:  10 February 2022

Thaís Leal-Silva
Affiliation:
Laboratory of Immunology and Genomics of Parasites, Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil Post-graduation Program in Health Sciences: Infectious Diseases and Tropical Medicine, Faculdade de Medicina, Federal University of Minas Gerais, Belo Horizonte, Brazil
Camila de Almeida Lopes
Affiliation:
Laboratory of Immunology and Genomics of Parasites, Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
Flaviane Vieira-Santos
Affiliation:
Laboratory of Immunology and Genomics of Parasites, Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
Fabrício Marcus Silva Oliveira
Affiliation:
Laboratory of Immunology and Genomics of Parasites, Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
Lucas Kraemer
Affiliation:
Laboratory of Immunology and Genomics of Parasites, Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
Luiza de Lima Silva Padrão
Affiliation:
Laboratory of Immunology and Genomics of Parasites, Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil Post-graduation Program in Health Sciences: Infectious Diseases and Tropical Medicine, Faculdade de Medicina, Federal University of Minas Gerais, Belo Horizonte, Brazil
Chiara Cássia Oliveira Amorim
Affiliation:
Laboratory of Immunology and Genomics of Parasites, Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
Jorge Lucas Nascimento Souza
Affiliation:
Laboratory of Immunology and Genomics of Parasites, Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
Fernando Sérgio Barbosa
Affiliation:
Laboratory of Immunology and Genomics of Parasites, Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
Milene Alvarenga Rachid
Affiliation:
Laboratory of Protozooses, Department of General Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
Remo Castro Russo
Affiliation:
Laboratory of Pulmonary Immunology and Mechanics, Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
Ricardo Toshio Fujiwara
Affiliation:
Laboratory of Immunology and Genomics of Parasites, Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil Post-graduation Program in Health Sciences: Infectious Diseases and Tropical Medicine, Faculdade de Medicina, Federal University of Minas Gerais, Belo Horizonte, Brazil
Lilian Lacerda Bueno*
Affiliation:
Laboratory of Immunology and Genomics of Parasites, Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil Post-graduation Program in Health Sciences: Infectious Diseases and Tropical Medicine, Faculdade de Medicina, Federal University of Minas Gerais, Belo Horizonte, Brazil
*
Author for correspondence: Lilian Lacerda Bueno, E-mail: llbueno@icb.ufmg.br

Abstract

An increase in peripheral blood eosinophils in helminth infections is expected, and these cells are known to promote immunity against these parasites. However, studies have suggested that in some specific helminths, eosinophils may promote the needs and longevity of these parasites, and their role in these infections remains undefined, including in Toxocara canis infection. Thus, this study aimed to investigate the role of eosinophils in the context of larval migration of T. canis and the immunopathological aspects of infection. For this, we used wild-type mice and mice genetically deficient for the transcription factor GATA-binding factor 1 (GATA1−/−), infected with 1000 eggs of T. canis. At 0, 3, 14 and 63 days post-infection, parasite load, tissue cytokine production, leucocyte profile, bronchoalveolar lavage cells and histopathological analyses were carried out. Collectively, our results demonstrate that the presence of eosinophils mediates susceptibility to T. canis, inducing leucocytosis and the formation of granulomas, increasing the pulmonary and cerebral parasite load, and reducing the number of neutrophils, which may be necessary to control the infection.

Type
Research Article
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Ariyaratne, A and Finney, CAM (2019) Eosinophils and macrophages within the Th2-induced granuloma: balancing killing and healing in a tight space. Infection and Immunity 87, e00127-19.CrossRefGoogle Scholar
Barcelos, LS, Talvani, A, Teixeira, AS, Vieira, LQ, Cassali, GD, Andrade, SP and Teixeira, MM (2005) Impaired inflammatory angiogenesis, but not leukocyte influx, in mice lacking TNFR1. Journal of Leukocyte Biology 78, 352358.CrossRefGoogle Scholar
Fabre, V, Beiting, DP, Bliss, SK, Gebreselassie, NG, Gagliardo, LF, Lee, NA, Lee, JJ and Appleton, JA (2009) Eosinophil deficiency compromises parasite survival in chronic nematode infection. The Journal of Immunology 182, 15771583.CrossRefGoogle ScholarPubMed
Fan, C, Lin, Y, Hung, C, Chang, S and Su, K (2004) Enhanced inducible nitric oxide synthase expression and nitrotyrosine accumulation in experimental granulomatous hepatitis caused by Toxocara canis in mice. Parasite Immunology 26, 273281.CrossRefGoogle ScholarPubMed
Fattah, DI, Maizels, RM, McLaren, DJ and Spry, CJF (1986) Toxocara canis: interaction of human blood eosinophils with the infective larvae. Experimental Parasitology 61, 421431.CrossRefGoogle ScholarPubMed
Ferguson, BJ, Newland, SA, Gibbs, SE, Tourlomousis, P, Fernandes dos Santos, P, Patel, MN, Hall, SW, Walczak, H, Schramm, G, Haas, H, Dunne, DW, Cooke, A and Zaccone, P (2015) The Schistosoma mansoni T2 ribonuclease omega-1 modulates inflammasome-dependent IL-1β secretion in macrophages. International Journal for Parasitology 45, 809813.CrossRefGoogle ScholarPubMed
Foster, PS, Mould, AW, Yang, M, Mackenzie, J, Mattes, J, Hogan, SP, Mahalingam, S, Mckenzie, ANJ, Rothenberg, ME, Young, IG, Matthaei, KI and Webb, DC (2001) Elemental signals regulating eosinophil accumulation in the lung. Immunological Reviews 179, 173181.CrossRefGoogle ScholarPubMed
Gazzinelli-Guimarães, AC, Gazzinelli-Guimarães, PH, Nogueira, DS, Oliveira, FMS, Barbosa, FS, Amorim, CCO, Cardoso, MS, Kraemer, L, Caliari, MV, Akamatsu, MA, Ho, PL, Jones, KM, Weatherhead, J, Bottazzi, ME, Hotez, PJ, Zhan, B, Bartholomeu, DC, Russo, RC, Bueno, LL and Fujiwara, RT (2018) IgG induced by vaccination with Ascaris suum extracts is protective against infection. Frontiers in Immunology 9, 115.CrossRefGoogle ScholarPubMed
Gebreselassie, NG, Moorhead, AR, Fabre, V, Gagliardo, LF, Lee, NA, Lee, JJ and Appleton, JA (2012) Eosinophils preserve parasitic nematode larvae by regulating local immunity. The Journal of Immunology 188, 417425.CrossRefGoogle ScholarPubMed
Hagan, P, Wilkins, HA, Blumenthal, UJ, Hayes, RJ and Greenwood, BM (1985) Eosinophilia and resistance to Schistosoma haematobium in man. Parasite Immunology 6, 625632.CrossRefGoogle Scholar
Helmby, H and Grencis, RK (2004) Interleukin-1 plays a major role in the development of Th2-mediated immunity. European Journal of Immunology 34, 36743681.CrossRefGoogle Scholar
Hermosilla, C, Caro, TM, Silva, LMR, Ruiz, A and Taubert, A (2014) The intriguing host innate immune response: novel anti-parasitic defence by neutrophil extracellular traps. Parasitology 141, 14891498.CrossRefGoogle ScholarPubMed
Huang, L and Appleton, JA (2016) Eosinophils in helminth infection: defenders and dupes. Trends in Parasitology 32, 798807.CrossRefGoogle ScholarPubMed
Huang, L, Gebreselassie, NG, Gagliardo, LF, Ruyechan, MC, Luber, LK, Lee, NA, Lee, JJ and Appleton, JA (2015) Eosinophils mediate protective immunity against secondary nematode infection. Bone 23, 17.Google Scholar
Huwer, M, Sanft, S and Ahmed, JS (1989) Enhancement of neutrophil adherence to Toxocara canis larvae by the C3 component of complement and IgG antibodies. Zentralblatt fur Bakteriologie Mikrobiologie und Hygiene – Series A 270, 418423.CrossRefGoogle ScholarPubMed
Janecek, E, Beineke, A, Schnieder, T and Strube, C (2014) Neurotoxocarosis: marked preference of Toxocara canis for the cerebrum and T. cati for the cerebellum in the paratenic model host mouse. Parasites & Vectors 7, 113.CrossRefGoogle Scholar
Joice, SL, Mydeen, F, Couraud, PO, Weksler, BB, Romero, IA, Fraser, PA and Easton, AS (2009) Modulation of blood–brain barrier permeability by neutrophils: in vitro and in vivo studies. Brain Research 1298, 1323.CrossRefGoogle ScholarPubMed
Kaur, S, Bansal, Y, Kumar, R and Bansal, G (2020) A panoramic review of IL-6: structure, pathophysiological roles and inhibitors. Bioorganic and Medicinal Chemistry 28, 115327.CrossRefGoogle ScholarPubMed
Kayes, SG and Adams Oaks, J (1978) Development of the granulomatous response in murine toxocariasis. American Journal of Pathology 93, 277294.Google ScholarPubMed
Leal-Silva, T, Vieira-Santos, F, Oliveira, FMS, Padrão, LLS, Kraemer, L, da Paixão Matias, PH, de Almeida Lopes, C, Loiola Ruas, AC, de Azevedo, IC, Nogueira, DS, Rachid, MA, Caliari, MV, de Castro Russo, R, Fujiwara, RT and Bueno, LL (2021) Detrimental role of IL-33/ST2 pathway sustaining a chronic eosinophil-dependent Th2 inflammatory response, tissue damage and parasite burden during Toxocara canis infection in mice. PLoS Neglected Tropical Diseases 15, 125.CrossRefGoogle ScholarPubMed
Liao, C-W, Fan, C-K, Kao, T-C, Ji, D-D, Su, K-E, Lin, Y-H and Cho, W-L (2008) Brain injury-associated biomarkers of TGF-beta1, S100B, GFAP, NF-L, tTG, AbetaPP, and tau were concomitantly enhanced and the UPS was impaired during acute brain injury caused by Toxocara canis in mice. BMC Infectious Diseases 8, 1–15.CrossRefGoogle ScholarPubMed
Liu, YW, Li, S and Dai, SS (2018) Neutrophils in traumatic brain injury (TBI): friend or foe? Journal of Neuroinflammation 15, 118.CrossRefGoogle ScholarPubMed
Nagy, D, Bede, O, Danka, J, Szénási, Z and Sipka, S (2012) Analysis of serum cytokine levels in children with chronic cough associated with Toxocara canis infection. Parasite Immunology 34, 581588.CrossRefGoogle ScholarPubMed
Natoli, G and Ostuni, R (2019) Adaptation and memory in immune responses. Nature Immunology 20, 783792.CrossRefGoogle ScholarPubMed
Ng, LG, Ostuni, R and Hidalgo, A (2019) Heterogeneity of neutrophils. Nature Reviews Immunology 19, 255265.CrossRefGoogle ScholarPubMed
Nogueira, DS, Gazzinelli-Guimarães, PH, Barbosa, FS, Resende, NM, Silva, CC, de Oliveira, LM, Amorim, CCO, Oliveira, FMS, Mattos, MS, Kraemer, LR, Caliari, MV, Gaze, S, Bueno, LL, Russo, RC and Fujiwara, RT (2016) Multiple exposures to Ascaris suum induce tissue injury and mixed Th2/Th17 immune response in mice. PLoS Neglected Tropical Diseases 10, 119.CrossRefGoogle ScholarPubMed
Obata-Ninomiya, K, Domeier, PP and Ziegler, SF (2020) Basophils and eosinophils in nematode infections. Frontiers in Immunology 11, 112.CrossRefGoogle ScholarPubMed
Oliveira, FMS, Matias, PHP, Kraemer, L, Gazzinelli-Guimarães, AC, Santos, FV, Amorim, CCO, Nogueira, DS, Freitas, CS, Caliari, MV, Bartholomeu, DC, Bueno, LL, Russo, RC and Fujiwara, RT (2019) Comorbidity associated to Ascaris suum infection during pulmonary fibrosis exacerbates chronic lung and liver inflammation and dysfunction but not affect the parasite cycle in mice. PLoS Neglected Tropical Diseases 13, 130.CrossRefGoogle Scholar
Pecinali, NR, Gomes, RN, Amendoeira, FC, Bastos, ACMP, Martins, MJQA, Pegado, CS, Bastos, OMP, Bozza, PT and Castro-Faria-Neto, HC (2005) Influence of murine Toxocara canis infection on plasma and bronchoalveolar lavage fluid eosinophil numbers and its correlation with cytokine levels. Veterinary Parasitology 134, 121130.CrossRefGoogle ScholarPubMed
Rankin, SM, Conroy, DM and Williams, TJ (2000) Eotaxin and eosinophil recruitment: implications for human disease. Molecular Medicine Today 6, 2027.CrossRefGoogle ScholarPubMed
Resende, NM, Gazzinelli-Guimarães, PH, Barbosa, FS, Oliveira, LM, Nogueira, DS, Gazzinelli-Guimarães, AC, Gonçalves, MTP, Amorim, CCO, Oliveira, FMS, Caliari, MV, Rachid, MA, Volpato, GT, Bueno, LL, Geiger, SM and Fujiwara, RT (2015) New insights into the immunopathology of early Toxocara canis infection in mice. Parasites & Vectors 8, 354.CrossRefGoogle ScholarPubMed
Rodolpho, JMA, Oliveira, SRP, Souza, LC, Dejani, NN, Neris, DM, Correia, RO, Zaia, MG, Faccioli, LH, Melo, DG and Anibal, FF (2014) Expression of the costimulatory molecules CD80, C86 and MHC II in eosinophil, during the peak of eosinophilia in the syndrome larvas migrans. Bio Technology 66, 2021620221.Google Scholar
Rosenberg, HF, Dyer, KD and Foster, PS (2013) Eosinophils: changing perspectives in health and disease. Nature Reviews Immunology 13, 922.CrossRefGoogle ScholarPubMed
Rostami, A, Riahi, SM, Holland, CV, Taghipour, A, Khalili-Fomeshi, M, Fakhri, Y, Omrani, VF, Hotez, PJ and Gasser, RB (2019) Seroprevalence estimates for toxocariasis in people worldwide: a systematic review and meta-analysis. PLoS Neglected Tropical Diseases 13, e0007809.CrossRefGoogle ScholarPubMed
Rothenberg, ME and Hogan, SP (2006) The eosinophil. Annual Review of Immunology 24, 147174.CrossRefGoogle ScholarPubMed
Sales, F, Tristão, M, Rocha, FA, Carlos, D, Ketelut-carneiro, N, Oliveira, C, Souza, S, Milanezi, CM, Silva, JS and Hube, B (2017) Th17-inducing cytokines IL-6 and IL-23 are crucial for granuloma formation during experimental paracoccidioidomycosis, 8, 949.CrossRefGoogle Scholar
Saraiva, M and O'Garra, A (2010) The regulation of IL-10 production by immune cells. Nature Reviews Immunology 10, 170181.CrossRefGoogle ScholarPubMed
Swartz, JM, Dyer, KD, Cheever, AW, Ramalingam, T, Pesnicak, L, Domachowske, JB, Lee, JJ, Lee, NA, Foster, PS, Wynn, TA and Rosenberg, HF (2006) Schistosoma mansoni infection in eosinophil lineage-ablated mice. Blood 108, 24202427.CrossRefGoogle ScholarPubMed
Weller, PF and Spencer, LA (2017) Functions of tissue-resident eosinophils. Nature Reviews Immunology 17, 746760.CrossRefGoogle ScholarPubMed
Yu, C, Cantor, AB, Yang, H, Browne, C, Wells, RA, Fujiwara, Y and Orkin, SH (2002) Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo. Journal of Experimental Medicine 195, 13871395.CrossRefGoogle ScholarPubMed