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Spleen atrophy related immune system changes attributed to infection of Angiostrongylus cantonensis in mouse model

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Abstract

The spleen is one of the most important peripheral immune organs, which is frequently affected in infectious diseases. Infectious diseases can induce splenic alterations including splenic atrophy and functional alteration, while splenic atrophy may in turn interferes with recovery of infectious diseases. Angiostrongyliasis is an infectious disease by Angiostrongylus cantonensis (A. cantonensis), which invade non-permissive hosts, such as humans and mice, to cause severe damage to the central nervous system (CNS) and acute inflammatory response. A. cantonensis infection-induced CNS injury has been confirmed to be due to profound immunopathology derived from peripheral immune components. However, the mechanism of immunopathology remains largely unknown. Here, we found that A. cantonensis invaded non-permissive hosts such as mice in the brain, but not in the other peripheral organs. However, this infection induced severe spleen atrophy. We further recognized that this atrophy is associated with a decrease of total splenocyte number and disruption of splenic structure due to reduced proliferation and increased apoptotosis. These also resulted in deterioration of T cell profile in the periphery with a low CD4/CD8 ratio and B/T cell ratio, and increased ratio of CD4+CD25+Foxp3+ Treg, CD8+CD28 T, and CD38+T lymphocyte of spleen. Albendazole treatment can alleviate spleen atrophy and set T cell immune reconstitution in some extend. Our data showed that A. cantonensis infection can cause splenic atrophy. These results are suggested to put more emphasis to improve the function of immune system. Meanwhile, infection and treatment model will be useful to evaluate new therapeutic approaches which can prevent or reverse immunosuppression and infectious complications.

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Abbreviations

CNS:

Central nervous system

Dpi:

Day post infection

References

  • Awaad A, Moustafa AY (2016) Immunotoxicity of skin acid secretion produced by the sea slug Berthellina citrina in mice spleen: histological and Immunohistochemical study. Acta Histochem 118:596–605

    Article  CAS  PubMed  Google Scholar 

  • Baheti NN, Sreedharan M, Krishnamoorthy T, Nair MD, Radhakrishnan K (2009) Eosinophilic meningitis and an ocular worm in a patient from Kerala, south India. BMJ Case Rep 2009:bcr2007122093

    CAS  PubMed  PubMed Central  Google Scholar 

  • Balogh P, Horvath G, Szakal AK (2004) Immunoarchitecture of distinct reticular fibroblastic domains in the white pulp of mouse spleen. J Histochem Cytochem 52:1287–1298

    Article  CAS  PubMed  Google Scholar 

  • Barratt J et al (2016) Angiostrongylus cantonensis: a review of its distribution, molecular biology and clinical significance as a human pathogen. Parasitology 143:1087–1118

    Article  PubMed  Google Scholar 

  • Brendolan A, Rosado MM, Carsetti R, Selleri L, Dear TN (2007) Development and function of the mammalian spleen. Bioessays 29:166–177

    Article  CAS  PubMed  Google Scholar 

  • Brousse V, Buffet P, Rees D (2014) The spleen and sickle cell disease: the sick(led) spleen. Br J Haematol 166:165–176

    Article  PubMed  Google Scholar 

  • Cesta MF (2006) Normal structure, function, and histology of the spleen. Toxicol Pathol 34:455–465

    Article  PubMed  Google Scholar 

  • Chen AL et al (2014) The quantitative and functional changes of NK cells in mice infected with Angiostrongylus cantonensis. Parasitol Res 113:2087–2094

    Article  PubMed  Google Scholar 

  • Cortesini R, LeMaoult J, Ciubotariu R, Cortesini NS (2001) CD8+CD28 T suppressor cells and the induction of antigen-specific, antigen-presenting cell-mediated suppression of Th reactivity. Immunol Rev 182:201–206

    Article  CAS  PubMed  Google Scholar 

  • Diao Z, Chen X, Yin C, Wang J, Qi H, Ji A (2009) Angiostrongylus cantonensis: effect of combination therapy with albendazole and dexamethasone on Th cytokine gene expression in PBMC from patients with eosinophilic meningitis. Exp Parasitol 123:1–5

    Article  CAS  PubMed  Google Scholar 

  • Dillon AM, Stein HB, English RA (1982) Splenic atrophy in systemic lupus erythematosus. Ann Intern Med 96:40–43

    Article  CAS  PubMed  Google Scholar 

  • Elmore SA (2006) Enhanced histopathology of the spleen. Toxicol Pathol 34:648–655

    Article  PubMed  PubMed Central  Google Scholar 

  • Feng Y et al (2014) The pathogenesis of optic neuritis caused by Angiostrongylus cantonensis in BALB/c mice. Parasites Vectors 7:339

    Article  PubMed  PubMed Central  Google Scholar 

  • Gadani SP, Walsh JT, Lukens JR, Kipnis J (2015) Dealing with danger in the CNS: the response of the immune system to injury. Neuron 87:47–62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giulia P et al (2016) Brain atrophy, anti-smooth muscle antibody and cognitive impairment: an association study. Aging Dis 7:318–325

    Article  PubMed  Google Scholar 

  • Gomez-Perez GP, van Bruggen R, Grobusch MP, Dobano C (2014) Plasmodium falciparum malaria and invasive bacterial co-infection in young African children: the dysfunctional spleen hypothesis. Malar J 13:335

    Article  PubMed  PubMed Central  Google Scholar 

  • Higashida H, Yokoyama S, Huang JJ, Liu L, Ma WJ, Akther S, Higashida C, Kikuchi M, Minabe Y, Munesue T (2012) Social memory, amnesia, and autism: brain oxytocin secretion is regulated by NAD+ metabolites and single nucleotide polymorphisms of CD38. Neurochem Int 61:828–838

    Article  CAS  PubMed  Google Scholar 

  • Intapan PM, Kittimongkolma S, Niwattayakul K, Sawanyawisuth K, Maleewong W (2008) Cerebrospinal fluid cytokine responses in human eosinophilic meningitis associated with angiostrongyliasis. J Neurol Sci 267:17–21

    Article  CAS  PubMed  Google Scholar 

  • Lee JD, Wang JJ, Chang JH, Chung LY, Chen ER, Yen CM (1996) Role of T cell subpopulations in mice infected with Angiostrongylus cantonensis. J Helminthol 70:211–214

    Article  CAS  PubMed  Google Scholar 

  • Liu H, Luo X, Shen E, Li H, Ding X, Chen D (2013) Alteration of T cell subtypes in spleen and antibodies of serum in mice infected with Angiostrongylus cantonensis. Parasitol Res 112:1255–1260

    Article  PubMed  Google Scholar 

  • Malavasi F, Deaglio S, Damle R, Cutrona G, Ferrarini M, Chiorazzi N (2011) CD38 and chronic lymphocytic leukemia: a decade later. Blood 118:3470–3478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Malek TR, Bayer AL (2004) Tolerance, not immunity, crucially depends on IL-2. Nat Rev Immunol 4:665–674

    Article  CAS  PubMed  Google Scholar 

  • Medina KL (2016) Overview of the immune system. Handb Clin Neurol 133:61–76

    Article  PubMed  Google Scholar 

  • Morelli AE et al (2003) Internalization of circulating apoptotic cells by splenic marginal zone dendritic cells: dependence on complement receptors and effect on cytokine production. Blood 101:611–620

    Article  CAS  PubMed  Google Scholar 

  • Nolte MA, Hamann A, Kraal G, Mebius RE (2002) The strict regulation of lymphocyte migration to splenic white pulp does not involve common homing receptors. Immunology 106:299–307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oldenhove G et al (2009) Decrease of Foxp3+ Treg cell number and acquisition of effector cell phenotype during lethal infection. Immunity 31:772–786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Onyema OO, Njemini R, Forti LN, Bautmans I, Aerts JL, De Waele M, Mets T (2015) Aging-associated subpopulations of human CD8+ T-lymphocytes identified by their CD28 and CD57 phenotypes. Arch Gerontol Geriat 61:494–502

    Article  CAS  Google Scholar 

  • OuYang L et al (2012) Differences of larval development and pathological changes in permissive and nonpermissive rodent hosts for Angiostrongylus cantonensis infection. Parasitol Res 111:1547–1557

    Article  PubMed  Google Scholar 

  • Peng H et al (2013) Interleukin 33 mediates type 2 immunity and inflammation in the central nervous system of mice infected with Angiostrongylus cantonensis. J Infect Dis 207:860–869

    Article  CAS  PubMed  Google Scholar 

  • Plitas G, Rudensky AY (2016) Regulatory T cells: differentiation and function. Cancer Immunol Res 4:721–725

    Article  CAS  PubMed  Google Scholar 

  • Salinas N, Olguin JE, Castellanos C, Saavedra R (2014) T cell suppression in vitro during Toxoplasma gondii infection is the result of IL-2 competition between Tregs and T cells leading to death of proliferating T cells. Scand J Immunol 79:1–11

    Article  CAS  PubMed  Google Scholar 

  • Smith DM, Nakazawa M, Freeman ML, Anderson CM, Oliveira MF, Little SJ, Gianella S (2016) Asymptomatic CMV Replication during Early HIV-infection is Associated with Lower CD4/CD8 Ratio during HIV Treatment. Clin Infect Dis doi:10.1093/cid/ciw612

  • Soares-Schanoski A et al (2012) Impaired antigen presentation and potent phagocytic activity identifying tumor-tolerant human monocytes. Biochem Biophys Res Commun 423:331–337

    Article  CAS  PubMed  Google Scholar 

  • Sojka DK, Bruniquel D, Schwartz RH, Singh NJ (2004) IL-2 secretion by CD4+ T cells in vivo is rapid, transient, and influenced by TCR-specific competition. J Immunol 172:6136–6143

    Article  CAS  PubMed  Google Scholar 

  • Spencer LA, Weller PF (2010) Eosinophils and Th2 immunity: contemporary insights. Immunol Cell Biol 88:250–256

    Article  PubMed  PubMed Central  Google Scholar 

  • Tenorio EP, Fernandez J, Castellanos C, Olguin JE, Saavedra R (2011) CD4+ Foxp3+ regulatory T cells mediate Toxoplasma gondii-induced T-cell suppression through an IL-2-related mechanism but independently of IL-10. Eur J Immunol 41:3529–3541

    Article  CAS  PubMed  Google Scholar 

  • Tu WC, Lai SC (2006) Angiostrongylus cantonensis: efficacy of albendazole-dexamethasone co-therapy against infection-induced plasminogen activators and eosinophilic meningitis. Exp Parasitol 113:8–15

    Article  CAS  PubMed  Google Scholar 

  • Walstra K, Gratwohl A, Riederer I, Speck B (1985) B/T cell ratio of rabbit peripheral blood lymphocytes. Influence of separation technique on results. J Immunol Methods 79:143–147

    Article  CAS  PubMed  Google Scholar 

  • Wang J et al (2013) Efficacy of tribendimidine against Angiostrongylus cantonensis infection in the mice. Parasitol Res 112:1039–1046

    Article  PubMed  Google Scholar 

  • Whitfield ML, George LK, Grant GD, Perou CM (2006) Common markers of proliferation. Nat Rev Cancer 6:99–106

    Article  CAS  PubMed  Google Scholar 

  • Yu L et al (2015) Preliminary expression profile of cytokines in brain tissue of BALB/c mice with Angiostrongylus cantonensis infection. Parasites Vectors 8:328

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The manuscript was revised by Md Robiul Karim, who is a postdoctoral fellow in Sun Yat-sen University. This work was supported in part by the National Key Research and Development Plan (2016YFC1200500), the National High Technology Research and Development Program of China (No. 2015AA020934), and the National Natural Science Foundation of China (81271855, 81261160324, 81401688).

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Correspondence to Xi Sun or Zhong-Dao Wu.

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Liu, Z., Wu, Y., Feng, Y. et al. Spleen atrophy related immune system changes attributed to infection of Angiostrongylus cantonensis in mouse model. Parasitol Res 116, 577–587 (2017). https://doi.org/10.1007/s00436-016-5322-9

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  • DOI: https://doi.org/10.1007/s00436-016-5322-9

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