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Increased early local immune responses and altered worm development in high-dose infections of mice susceptible to the filaria Litomosoides sigmodontis

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Abstract

The relationship between the number of larvae inoculated and filarial infection outcome is an important fundamental and epidemiological issue. Our study was carried out with BALB/c mice infected with the filaria Litomosoides sigmodontis. For the first time, an immunological analysis of infection with various doses was studied in parallel with parasitological data. Mice were inoculated with 200, 60 or 25 infective larvae (third stage larvae, L3), and monitored over 80 days. At 60 h post-inoculation the immune response was stronger in the 200 L3 group than the 25 L3 group. Cells from lymph nodes draining the site of inoculation proliferated intensely and produced large amounts of IL-5 and IL-4. In the pleural cavity, leukocyte populations accumulated earlier and in larger quantities. IgG1, IL-4 and IL-10 serum concentrations were transiently higher. During the first 10 days the worm recovery rates were identical in all groups, but decreased thereafter in the 200 L3 group. In this group, the development of the worms was altered, with reduced lengths, diminished intra-uterine production of microfilariae and abnormalities of male copulatory organs. Whereas mice inoculated with 25 L3 became microfilaraemic, only one third reached patency in the 200 L3 group. However, detrimental effects of high numbers of worms are not seen in studies using different inoculation protocols. This suggests that the very early events determine subsequent immune response and infection outcome rather than competitive interactions between the worms.

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References

  1. Akue JP, Egwang TG, Devaney E (1994) High levels of parasite-specific IgG4 in the absence of microfilaremia in Loa loa infection. Trop Med Parasitol 45:246–248

    CAS  PubMed  Google Scholar 

  2. Al-Qaoud KM, Taubert A, Zahner H, Fleischer B, Hoerauf A (1997) Infection of BALB/c mice with the filarial nematode Litomosoides sigmodontis: role of CD4+ T cells in controlling larval development. Infect Immun 65:2457–2461

    CAS  PubMed  Google Scholar 

  3. Al-Qaoud KM, Fleischer B, Hoerauf A (1998) The Xid defect imparts susceptibility to experimental murine filariosis—association with a lack of antibody and IL-10 production by B cells in response to phosphorylcholine. Int Immunol 10:17–25

    Article  CAS  PubMed  Google Scholar 

  4. Al-Qaoud KM, Pearlman E, Hartung T, Klukowski J, Fleischer B, Hoerauf A (2000) A new mechanism for IL-5-dependent helminth control: neutrophil accumulation and neutrophil-mediated worm encapsulation in murine filariasis are abolished in the absence of IL-5. Int Immunol 12:899–908

    Article  CAS  PubMed  Google Scholar 

  5. Allen JE, Daub J, Guiliano D, McDonnell A, Lizotte-Waniewski M, Taylor DW, Blaxter M (2000) Analysis of genes expressed at the infective larval stage validates utility of Litomosoides sigmodontis as a murine model for filarial vaccine development. Infect Immun 68:5454–5458

    Article  CAS  PubMed  Google Scholar 

  6. Babayan S, Ungeheuer MN, Martin C, Attout T, Belnoue E, Snounou G, Renia L, Korenaga M, Bain O (2003) Resistance and susceptibility to filarial infection with Litomosoides sigmodontis are associated with early differences in parasite development and in localized immune reactions. Infect Immun 71:6820–6829

    Article  CAS  PubMed  Google Scholar 

  7. Baize S, Wahl G, Soboslay PT, Egwang TG, Georges AJ (1997) T helper responsiveness in human Loa loa infection; defective specific proliferation and cytokine production by CD4+ T cells from microfilaraemic subjects compared with amicrofilaraemics. Clin Exp Immunol 108:272–278

    Article  CAS  PubMed  Google Scholar 

  8. Basanez MG, Collins RC, Porter CH, Little MP, Brandling-Bennett D (2002) Transmission intensity and the patterns of Onchocerca volvulus infection in human communities. Am J Trop Med Hyg 67:669–679

    PubMed  Google Scholar 

  9. Breton B, Diagne M, Wanji S, Bougnoux ME, Chandre F, Marechal P, Petit G, Vuong PN, Bain O (1997) Ivermectin and moxidectin in two filarial systems: resistance of Monanema martini; inhibition of Litomosoides sigmodontis insemination. Parassitologia 39:19–28

    CAS  PubMed  Google Scholar 

  10. Connal A, Connal SLM (1922) The development of Loa loa (Guyot) in Chrysops silacea (Austen) and Chrysops dimidiata (Van der Wulp). Trans R Soc Trop Med Hyg 46:64–89

    Google Scholar 

  11. Cook RL, Roberts LS (1991) In vivo effects of putative crowding factors on development of Hymenolepis diminuta. J Parasitol 77:21–25

    Google Scholar 

  12. Dhar DN, Singha P (1971) Studies on quantitative infections of Litomosoides carinii (Travassos, 1919) in white rats. Z Tropenmed Parasitol 22:312–325

    CAS  PubMed  Google Scholar 

  13. Diagne M, Petit G, Liot P, Cabaret J, Bain O (1990) The filaria Litomosoides galizai in mites; microfilarial distribution in the host and regulation of the transmission. Ann Parasitol Hum Comp 65:193–199

    CAS  PubMed  Google Scholar 

  14. Fain A (1981) Epidemiology and pathology of loaiasis. Ann Soc Belg Med Trop 61:277–285

    CAS  PubMed  Google Scholar 

  15. Gillespie RD, Mbow ML, Titus RG (2000) The immunomodulatory factors of bloodfeeding arthropod saliva. Parasite Immunol 22:319–331

    Article  CAS  PubMed  Google Scholar 

  16. Gordon RM, Crewe W (1953) The deposition of the infective stage of Loa loa by Chrysops silacea, and the early stages of its migration to the deeper tissues of the mammalian host. Ann Trop Med Parasitol 47:74–85

    CAS  PubMed  Google Scholar 

  17. Gray CA, Lawrence RA (2002) A role for antibody and Fc receptor in the clearance of Brugia malayi microfilariae. Eur J Immunol 32:1114–1120

    Article  CAS  PubMed  Google Scholar 

  18. Haque A, Lefebvre MN, Ogilvie BM, Capron A (1978) Dipetalonema viteae in hamsters: effect of antiserum or immunization with parasite extracts on production of microfilariae. Parasitology 76:61–75

    CAS  PubMed  Google Scholar 

  19. Hawking F (1954) The reproductive system of Litomosoides carinii, a filarial parasite of cotton rat. III. The number of microfilariae produced. Ann Trop Med Parasitol 48:382–385

    PubMed  Google Scholar 

  20. Hoffmann WH, Pfaff AW, Schulz-Key H, Soboslay PT (2001) Determinants for resistance and susceptibility to microfilaraemia in Litomosoides sigmodontis filariasis. Parasitology 122:641–649

    Article  CAS  PubMed  Google Scholar 

  21. Lal RB, Paranjape RS, Briles DE, Nutman TB, Ottesen EA (1987) Circulating parasite antigen(s) in lymphatic filariasis: use of monoclonal antibodies to phosphocholine for immunodiagnosis. J Immunol 138:3454–3460

    CAS  PubMed  Google Scholar 

  22. Lavoipierre MM (1958) Studies on the host-parasite relationships of filarial nematodes and their arthropod hosts. I. The sites of development and the migration of Loa loa in Chrysops silacea, the escape of the infective forms from the head of the fly, and the effect of the worm on its insect host. Ann Trop Med Parasitol 52:103–121

    CAS  PubMed  Google Scholar 

  23. Lawrence RA (1996) Lymphatic filariasis: what mice can tell us. Parasitol Today 12:267–271

    Article  Google Scholar 

  24. Le Goff L, Maréchal P, Petit G, Taylor DW, Hoffmann W, Bain O (1997) Early reduction of the challenge recovery rate following immunization with irradiated infective larvae in a filaria mouse system. Trop Med Int Health 2:1170–1174

    Article  PubMed  Google Scholar 

  25. Le Goff L, Martin C, Oswald IP, Vuong PN, Petit G, Ungeheuer MN, Bain O (2000) Parasitology and immunology of mice vaccinated with irradiated Litomosoides sigmodontis larvae. Parasitology 120:271–280

    Article  PubMed  Google Scholar 

  26. Le Goff L, Loke P, Ali HF, Taylor DW, Allen JE (2000) Interleukin-5 is essential for vaccine-mediated immunity but not innate resistance to a filarial parasite. Infect Immun 68:2513–2517

    Article  PubMed  Google Scholar 

  27. Le Goff L, Lamb T, Graham A, Harcus Y, Allen J (2002) IL-4 is required to prevent filarial nematode development in resistant but not susceptible strains of mice. Int J Parasitol 32:1277

    Article  PubMed  Google Scholar 

  28. Maréchal P (1995) Deux filaires du genre Litomosoides chez la souris blanche; régulation du développement. Muséum National d’Histoire Naturelle, Paris, number 1995MNHN0018, p 89

  29. Maréchal P, Le Goff L, Petit G, Diagne M, Taylor DW, Bain O (1996) The fate of the filaria Litomosoides sigmodontis in susceptible and naturally resistant mice. Parasite 3:25–31

    PubMed  Google Scholar 

  30. Maréchal P, Le Goff L, Hoffman W, Rapp J, Oswald IP, Ombrouck C, Taylor DW, Bain O, Petit G (1997) Immune response to the filaria Litomosoides sigmodontis in susceptible and resistant mice. Parasite Immunol 19:273–279

    Article  PubMed  Google Scholar 

  31. Martin C, Al-Qaoud KM, Ungeheuer MN, Paehle K, Vuong PN, Bain O, Fleischer B, Hoerauf A (2000) IL-5 is essential for vaccine-induced protection and for resolution of primary infection in murine filariasis. Med Microbiol Immunol (Berl) 189:67–74

    Google Scholar 

  32. Martin C, Le Goff L, Ungeheuer MN, Vuong PN, Bain O (2000) Drastic reduction of a filarial infection in eosinophilic interleukin-5 transgenic mice. Infect Immun 68:3651–3656

    Article  CAS  PubMed  Google Scholar 

  33. Martin C, Saeftel M, Vuong PN, Babayan S, Fischer K, Bain O, Hoerauf A (2001) B-cell deficiency suppresses vaccine-induced protection against murine filariasis but does not increase the recovery rate for primary infection. Infect Immun 69:7067–7073

    Article  CAS  PubMed  Google Scholar 

  34. Mbow ML, Bleyenberg JA, Hall LR, Titus RG (1998) Phlebotomus papatasi sand fly salivary gland lysate down-regulates a Th1, but up-regulates a Th2, response in mice infected with Leishmania major. J Immunol 161:5571–5577

    CAS  PubMed  Google Scholar 

  35. Orihel TC, Eberhard ML (1985) Loa loa: development and course of patency in experimentally-infected primates. Trop Med Parasitol 36:215–224

    CAS  PubMed  Google Scholar 

  36. Paterson S, Viney ME (2002) Host immune responses are necessary for density dependence in nematode infections. Parasitology 125:283–292

    Article  CAS  PubMed  Google Scholar 

  37. Petit G, Diagne M, Marechal P, Owen D, Taylor D, Bain O (1992) Maturation of the filaria Litomosoides sigmodontis in BALB/c mice; comparative susceptibility of nine other inbred strains. Ann Parasitol Hum Comp 67:144–150

    CAS  PubMed  Google Scholar 

  38. Pfarr KM, Fischer K, Hoerauf A (2003) Involvement of Toll-like receptor 4 in the embryogenesis of the rodent filaria Litomosoides sigmodontis. Med Microbiol Immunol (Berl) 192:53–56

    Google Scholar 

  39. Saeftel M, Volkmann L, Korten S, Brattig N, Al-Qaoud K, Fleischer B, Hoerauf A (2001) Lack of interferon-gamma confers impaired neutrophil granulocyte function and imparts prolonged survival of adult filarial worms in murine filariasis. Microbes Infect 3:203–213

    Article  CAS  PubMed  Google Scholar 

  40. Saeftel M, Arndt M, Specht S, Volkmann L, Hoerauf A (2003) Synergism of gamma interferon and interleukin-5 in the control of murine filariasis. Infect Immun 71:6978–6985

    Article  CAS  PubMed  Google Scholar 

  41. Schoeler GB, Wikel SK (2001) Modulation of host immunity by haematophagous arthropods. Ann Trop Med Parasitol 95:755–771

    Article  CAS  PubMed  Google Scholar 

  42. Schulz-Key H (1987) Ivermectin in the treatment of onchocerciasis. In: ISI Atlas of Science: Pharmacology. ISI-Press, Philadelphia, pp 246–249

  43. Simonsen PE, Meyrowitsch DW, Jaoko WG, Malecela MN, Mukoko D, Pedersen EM, Ouma JH, Rwegoshora RT, Masese N, Magnussen P, Estambale BB, Michael E (2002) Bancroftian filariasis infection, disease, and specific antibody response patterns in a high and a low endemicity community in East Africa. Am J Trop Med Hyg 66:550–559

    PubMed  Google Scholar 

  44. Söffner J, Wenk P (1985) Wirkung von Ivermectin auf die Verteilung der Mikrofilarien in den Organen und auf die Embryogenese bei der Baumwollrattenfilariae Litomosoides carinii (Nematoda: Filarioidea). Mitt Österr Tropenmed Parasit 7:229–234

  45. Taubert A, Zahner H (2001) Cellular immune responses of filaria (Litomosoides sigmodontis) infected BALB/c mice detected on the level of cytokine transcription. Parasite Immunol 23:453–462

    Article  CAS  PubMed  Google Scholar 

  46. Volkmann L, Saeftel M, Bain O, Fischer K, Fleischer B, Hoerauf A (2001) Interleukin-4 is essential for the control of microfilariae in murine infection with the filaria Litomosoides sigmodontis. Infect Immun 69:2950–2956

    Article  CAS  PubMed  Google Scholar 

  47. Volkmann L, Bain O, Saeftel M, Specht S, Fischer K, Brombacher F, Matthaei KI, Hoerauf A (2003) Murine filariasis: interleukin 4 and interleukin 5 lead to containment of different worm developmental stages. Med Microbiol Immunol (Berl) 192:23–31

    Google Scholar 

  48. Wahl G, Georges AJ (1995) Current knowledge on the epidemiology, diagnosis, immunology, and treatment of loiasis. Trop Med Parasitol 46:287–291

    CAS  PubMed  Google Scholar 

  49. Wanji S, Cabaret J, Gantier JC, Bonnand N, Bain O (1990) The fate of the filaria Monanema martini in two rodent hosts: recovery rate, migration, and localization. Ann Parasitol Hum Comp 65:80–88

    CAS  PubMed  Google Scholar 

  50. Wanji S, Gantier JC, Petit G, Rapp J, Bain O (1994) Monanema martini in its murid hosts: microfiladermia related to infective larvae and adult filariae. Trop Med Parasitol 45:107-111

    CAS  PubMed  Google Scholar 

  51. Weiss N (1978) Studies on Dipetalonema viteae (Filarioidea). I. Microfilaraemia in hamsters in relation to worm burden and humoral immune response. Acta Trop 35:137–150

    CAS  PubMed  Google Scholar 

  52. Wenk P, Wegerhof PH (1982) Studies on acquired resistance of the cotton rat against microfilariae of Litomosoides carinii. 2. Injection of microfilariae during prepatency. Z Parasitenkd 68:321–329

    CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to thank Dr. Judith E. Allen for her insightful comments on the manuscript, Jean-Christophe Deschemins at the Institut Cochin for his help and patience with the FACS machine, and Andrea Graham for her help with the regression analysis choice. A.H. received financial support from the German Research Foundation (grant Ho2009/1–3). A.H. and O.B. received financial support from the European Commission (grant ICA4–1999–10002).

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Author notes

  1. Simon Babayan

    Present address: Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh, UK

  2. Achim Hoerauf

    Present address: Institute of Medical Parasitology, University Clinic Bonn, Bonn, Germany

  3. Coralie Martin

    Present address: Leukocyte Biology Section, Division of Biomedical Sciences, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London, UK

Authors and Affiliations

  1. Parasitologie Comparée et Modèles expérimentaux associé à INSERM U567 et Ecole Pratique des Hautes Etudes, Muséum National d’Histoire Naturelle, 61 rue Buffon, 75213, Paris Cedex 05, France

    Simon Babayan, Tarik Attout, Odile Bain & Coralie Martin

  2. Bernhard-Nocht-Institute of Tropical Medecine, Hamburg, Germany

    Sabine Specht & Achim Hoerauf

  3. Unité de Parasitologie Biomédicale, Institut Pasteur, Paris, France

    Georges Snounou

  4. Département d’Immunologie, Institut Cochin, INSERM U567, CNRS UMR 8104, Université René Descartes, Hôpital Cochin, Paris, France

    Laurent Rénia

  5. Department of Parasitology, Kochi Medical School, Nankoku City, Kochi, Japan

    Masataka Korenaga

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  1. Simon Babayan
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Correspondence to Odile Bain.

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Babayan, S., Attout, T., Specht, S. et al. Increased early local immune responses and altered worm development in high-dose infections of mice susceptible to the filaria Litomosoides sigmodontis. Med Microbiol Immunol 194, 151–162 (2005). https://doi.org/10.1007/s00430-004-0226-1

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