Hostname: page-component-cd9895bd7-7cvxr Total loading time: 0 Render date: 2024-12-27T12:48:00.142Z Has data issue: false hasContentIssue false
  • English
  • Français

The migration of Ascaris suum larvae, and the associated pulmonary inflammatory response in susceptible C57BL/6j and resistant CBA/Ca mice

Published online by Cambridge University Press:  23 March 2007

R. Lewis ,
J. M. Behnke ,
J. P. Cassidy ,
P. Stafford ,
N. Murray  and
C. V. Holland
R. Lewis
Affiliation:
School of Natural Sciences, Department of Zoology, Trinity College, University of Dublin, Dublin 2, Ireland
J. M. Behnke
Affiliation:
School of Biology, University of Nottingham, University Park, Nottingham NG7 2RD, UK
J. P. Cassidy
Affiliation:
Department of Veterinary Pathology, University College Dublin, Belfield, Dublin 4, Ireland
P. Stafford
Affiliation:
School of Natural Sciences, Department of Zoology, Trinity College, University of Dublin, Dublin 2, Ireland
N. Murray
Affiliation:
School of Natural Sciences, Department of Zoology, Trinity College, University of Dublin, Dublin 2, Ireland
C. V. Holland*
Affiliation:
School of Natural Sciences, Department of Zoology, Trinity College, University of Dublin, Dublin 2, Ireland
*
*Corresponding author: School of Natural Sciences, Department of Zoology, Trinity College, University of Dublin, Dublin 2, Ireland. Tel: +353 (1) 896 1096. Fax: +353 (1) 677 8094. E-mail: cholland@tcd.ie
Get access Rights & Permissions [Opens in a new window]

Summary

Ascariasis is an important infection in humans (Ascaris lumbricoides) and pigs (Ascaris suum) and individuals appear to be predisposed to either heavy or light worm burdens. These extremes of susceptibility and resistance are represented in a mouse model by 2 strains of mice, CBA mice showing high resistance to infection and C57BL/6 which are highly susceptible, as reflected in worm burdens in the lungs 6–7 days after infection. In an attempt to identify the point at which the difference between these 2 strains is first manifested, we quantified worm burdens at key stages during infection leading up to the pulmonary stage of development. Thus mice were inoculated with fully embryonated A. suum eggs and larval burdens were enumerated in the large intestine and rectum, liver and lungs of the 2 strains at 6 h post-inoculation (p.i.) and on each of days 1–8 p.i. inclusively. A higher percentage of the total inoculum was recovered from the intestine/rectum of C57BL/6j mice in contrast to CBA/Ca mice at 6 h p.i. Larvae were recovered from the intestinal contents and also whilst actively migrating through the large intestinal wall. The number of larvae recovered was significantly reduced in CBA/Ca mice in contrast to C57BL/6j mice between the phase of migration from the liver and arrival in the lungs. The combined results of the inoculation of mice with corticosteroids and the examination of the change in profile and number of leukocytes present in bronchoalveolar lavage fluid suggested that the pulmonary inflammatory immune response was not prominently involved in primary protection of mice to A. suum infection in the latter days of infection in the lungs. The susceptible C57BL/6j mice produced a BAL response almost twice as intense as that of resistant CBA/Ca mice with stronger neutrophil, lymphocyte and eosinophil but not macrophage components, suggesting that the difference in worm burdens between the strains was generated earlier in the course of infection. These results were further corroborated by a histological examination of the lung tissues which showed that the passage of the larval stages of A. suum through the mouse lungs was associated with a marked inflammatory response in both strains. Again, C57BL/6j mice exhibited increased inflammation relative to CBA/Ca mice. Hence some hepatic/post-hepatic factor that varies between the 2 strains, but exerts its effect before the lung phase plays a critical role in determining the success of larvae through the host tissues. The possible sites of this host defence are reviewed.

Keywords

Ascaris suummouse modelimmune responsebronchoalveolar lavageC57BL/6jCBA/Casusceptibilitylungsmigration
Type
Research Article
Information
Parasitology , Volume 134 , Issue 9 , August 2007 , pp. 1301 - 1314
Copyright
Copyright © Cambridge University Press 2007

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

Beaver, P. C. and Danaraj, T. J. (1958). Pulmonary ascariasis resembling eosinophilic lung. Autopsy report with description of larvae in bronchioles. American Journal of Tropical Medicine and Hygiene 7, 100–111.CrossRefGoogle ScholarPubMed
Behnke, J. M. and Parish, H. A. (1979). Nematospiroides dubuis: arrested development of larvae in immune mice. Experimental Parasitology 47, 116–127.CrossRefGoogle Scholar
Bindseil, E. (1970). Immunity to Ascaris. 3. The importance of gut immunity in mice. Acta Parasitologica et Microbiologica Scandinavica 78, 183–190.Google ScholarPubMed
Boes, J., Medley, G. F., Eriksen, L., Roepstorff, A. and Nansen, P. (1998). Distribution of Ascaris suum in experimentally and naturally infected pigs and comparison with Ascaris lumbricoides infections in humans. Parasitology 177, 589–596.CrossRefGoogle Scholar
Chan, M. S., Bundy, D. A. P. and Kan, S. P. (1993). Genetic relatedness as a determinant of predisposition to Ascaris lumbricoides and Trichuris trichiura infection. Parasitology 108, 77–80.CrossRefGoogle Scholar
Cooper, P. J., Chico, M. E., Sandoval, C., Espinel, I., Guevara, A., Kennedy, M. W., Urban, J. F. Jnr., Griffin, G. E. and Nutman, T. B. (2000). Human infection with Ascaris lumbricoides is associated with a polarised cytokine response. Journal of Infectious Diseases 182, 1207–1213.CrossRefGoogle ScholarPubMed
Crompton, D. W. T. and Tulley, J. J. (1987). How much ascariasis is there in Africa? Parasitology Today 3, 123–127.CrossRefGoogle ScholarPubMed
Crompton, D. W. T. (2001). Ascaris and Ascariasis. Advances in Parasitology 48, 285–375.CrossRefGoogle ScholarPubMed
Eriksen, L., Andersen, S., Nielsen, K., Pedersen, A. and Nielsen, J. (1980). Experimental Ascaris suum infection in pigs. Serological response, eosinophilia in peripheral blood, occurrence of white spots in the liver and worm recovery from the intestine. Nordisk Veterinærmedicin 32, 233–42.Google ScholarPubMed
Eriksen, L. (1981). Host-parasite relations of Ascaris suum infection in pigs and mice. Ph.D. thesis. Institute of Internal Medicine, Royal Veterinary and Agriculture University, Copenhagen.Google Scholar
Frontera, E., Roepstorff, A., Gázquez, A., Reina, D., Serrano, F. J. and Navarrete, I. (2003). Immunohistochemical distribution of antigens in the liver of infected and immunised pigs with Ascaris suum. Veterinary Parasitology 111, 9–18.CrossRefGoogle ScholarPubMed
Frontera, E., Roepstorff, A., Serrano, F. J., Gázquez, A., Reina, D. and Navarrete, I. (2004). Presence of immunoglobulins and antigens in serum, lung and small intestine in Ascaris suum infected and immunised pigs. Veterinary Parasitology 119, 59–71.CrossRefGoogle ScholarPubMed
Guyatt, H. L., Bundy, D. A. P., Medley, G. F. and Grenfell, B. T. (1990). The relationship between the frequency distribution of Ascaris lumbricoides and the prevalence and intensity of infection in human communities. Parasitology 101, 139–143.CrossRefGoogle ScholarPubMed
Hall, A. and Anwar, K. S. (1992). Intensity of reinfection with Ascaris lumbricoides and its implications for parasite control. Lancet 339, 1253–1257.CrossRefGoogle ScholarPubMed
Thein, HLAING (1993). Ascariasis and childhood malnutrition. Parasitology 107, S125–S136.Google Scholar
Holland, C. V., Asaolu, S. O., Crompton, D. W. T., Stoddart, R. C., Macdonald, R. and Torimiro, S. E. A. (1989). The epidemiology of Ascaris lumbricoides and other soil transmitted helminths in primary school children from Ile-Ife, Nigeria. Parasitology 99, 275–285.CrossRefGoogle ScholarPubMed
Holland, C. V. and Boes, J. (2002). Distributions and predisposition: people and pigs. In The Geohelminths: Ascaris, Trichuris and hookworm, Vol. 2 (ed. Holland, C. V. and Kennedy, M. W.), pp. 1–24. Kluwer Academic Publishers, Boston, Dordrecht and London.CrossRefGoogle Scholar
Johnstone, C., Leventhal, R. and Soulsby, E. J. L. (1978). The spin method for recovering tissue larvae and its use in evaluating C57BL/6 mice as a model for the study of resistance to infection with Ascaris suum. Journal of Parasitology 64, 1015–1020.CrossRefGoogle Scholar
Jungersen, G. (2002). Immunity and immune responses to Ascaris suum in pigs. In The Geohelminths: Ascaris, Trichuris and Hookworm, Vol. 2 (ed. Holland, C. V. and Kennedy, M. W.), pp. 105–124. Kluwer Academic Publishers, Boston, Dordrecht and London.CrossRefGoogle Scholar
Keller, A. E., Hillstrom, H. T. and Gass, R. S. (1932). The lungs of children with Ascaris: a roentgenologic study. Journal of American Medicine Abroad 99, 1249–1251.CrossRefGoogle Scholar
Kim, M., Kim, J. Y., Lim, J., Kim, Y., Han, K., Kang, C. S., Min, C. K., Kim, C. C., Lee, W. and Kim, B. K. (2002). Evaluation of early post-transplant leukocyte recovery using the undiluted erythrocyte lysing technique. Annals of Clinical and Laboratory Science 32, 159–163.Google ScholarPubMed
Lewis, R. (2006). The development of a mouse model to explore resistance and susceptibility to early Ascaris suum infection. Ph.D. thesis. The School of Natural Sciences, Department of Zoology, University of Dublin, Trinity College, Dublin.CrossRefGoogle Scholar
Lewis, R., Behnke, J. M., Stafford, P. and Holland, C. V. (2006). The development of a mouse model to explore resistance and susceptibility to early Ascaris suum infection. Parasitology 132, 289–300.CrossRefGoogle ScholarPubMed
Liljegren, C. H., Aalbæk, B., Nielsen, O. L. and Jensen, H. E. (2003). Some new aspects of the patholgy, pathogenesis, and aetiology of disseminated lung lesions in slaughter pigs. Acta Parasitologica et Microbiologica Scandinavica 111, 531–538.CrossRefGoogle Scholar
Loeffler, W. (1932). Zur Differentialdiagnose der Lungen-infiltrierungen. II Ueber flüchtige Succedanininfiltrate (mit Eosinophilie). Beiträge zur Klinik der Tuberkulose 79, 368–382.Google Scholar
Loeffler, W. (1956). Transient lung infiltrations with blood eosinophilia. International Archive of Allergy 8, 54–59.CrossRefGoogle Scholar
Matsuyama, W., Mizoguchi, A., Iwami, F., Kawabata, M. and Osame, M. (1998). A case of pulmonary infiltration with eosinophilia caused by Ascaris suum [Article in Japanese]. Nikon Kokyuki Gakkai Zasshi 36, 208–212.Google ScholarPubMed
McSharry, C., Xia, Y., Holland, C. V. and Kennedy, M. W. (1999). Natural immunity to Ascaris lumbricoides associated with immunoglobulin E antibody to ABA-1 allergen and inflammation indicators in children. Infection and Immunity 67, 484–489.CrossRefGoogle ScholarPubMed
Miquel, N., Roepstorff, A., Bailey, M. and Eriksen, L. (2005). Host immune reactions and worm kinetics during the expulsion of Ascaris suum in pigs. Parasite Immunology 27, 79–88.CrossRefGoogle ScholarPubMed
Mitchell, G. F., Hogarth-Scott, R. S., Edwards, R. D., Lewers, H. M., Cousins, G. and Moore, T. (1976). Studies on immune response to parasite antigens in mice. 1. Ascaris suum larvae numbers and antiphosphorylcholine responses in infected mice of various strains and in hypothymic nu/nu mice. International Archives of Allergy and Applied Immunity 52, 64–78.CrossRefGoogle Scholar
O'Lorcain, P. and Holland, C. V. (2000). The public health importance of Ascaris lumbricoides. Parasitology 121, S51–S71.CrossRefGoogle ScholarPubMed
Palmer, D. R., Hall, A., Hague, R. and Anwar, K. S. (1995). Antibody isotype responses to antigens of Ascaris lumbricoides in a case control study of persistently heavily infected children. Parasitology 111, 385–393.CrossRefGoogle Scholar
Peng, W., Zhou, X., Cui, X., Crompton, D. W. T., Whitehead, R. R., Xiong, J., Wu, H., Peng, J., Yang, Y., Wu, W., Xu, K. and Yan, Y. (1996). Ascaris, people and pigs in rural community of Jiangxi provience, China. Parasitology 113, 545–557.Google Scholar
Pérez, J., García, P. M., Mozos, E., Bautista, M. J. and Carrasco, L. (2001). Immunohistochemical characterization of hepatic lesions associated with migrating larvae of Ascaris suum in pigs. Journal of Comparative Pathology 124, 200–206.CrossRefGoogle ScholarPubMed
Roepstorff, A., Eriksen, L., Slotved, H.-C. and Nansen, P. (1997). Experimental Ascaris suum infection in the pig: worm population kinetics following single inoculations with three doses of infective eggs. Parasitology 115, 443–452.CrossRefGoogle ScholarPubMed
Ronéus, O. (1966). Studies on the aetiology and pathogenesis of white spots in the liver of pigs. Acta Veterinaria Scandinavica 7, 1–112.Google ScholarPubMed
Slotved, H.-C. (1997). Methods for quantitative recovery of larval and adult stages of nematodes (Ascaris suum and Oesophagostomum dentatum) in pigs and mice. Ph.D. thesis. Danish Centre for Experimental Parasitology. Royal Veterinary and Agriculture University, Copenhagen.Google Scholar
Slotved, H.-C., Eriksen, L., Murrell, K. D. and Nansen, P. (1997). Comparison of methods for recovery of Ascaris suum larvae from tissues of mice. International Journal for Parasitology 27, 1305–1310.CrossRefGoogle ScholarPubMed
Slotved, H.-C., Eriksen, L., Murrell, K. D. and Nansen, P. (1998). Early Ascaris suum migration in mice as a model for pigs. Journal of Parasitology 84, 16–18.CrossRefGoogle Scholar
Spillmann, R. K. (1975). Pulmonary ascariasis in tropical communities. The American Journal of Tropical Medicine and Hygiene 25, 791–800.CrossRefGoogle Scholar
Taffs, L. F. (1968). Immunological studies on experimental infection of guinea pigs and rabbits with Ascaris suum Goeze, 1782. IV. The histopathology of the liver and lung. Journal of Helminthology 39, 297–302.CrossRefGoogle Scholar
Tjørnehøj, K., Eriksen, L., Aalbæk, B. and Nansen, P. (1992). Interaction between Ascaris suum and Pastuerella multocida in the lungs of mice. Parasitology Research 78, 525–528.CrossRefGoogle Scholar
Vogel, H. and Minning, W. (1942). Beiträge zur Klinik der Lungen-ascariasis und zur Frage der flüchtigen, eosinophilen Lungeninfiltrate. Beiträge zur Klinik der Tuberkulose 98, 620–654.CrossRefGoogle Scholar
Wahid, F. N. and Behnke, J. M. (1996). Genetic control of acquired resistance to Heligmosomoides polygyrus: overcoming genetically determined weak responder status by strategic immunization with ivermectin-abbreviated infection. Journal of Helminthology 70, 159–168.CrossRefGoogle Scholar
Wakelin, D. (1996). Immunity to Parasites: How Parasitic Infections are Controlled, 2 Edn. Cambridge University Press, Cambridge.Google Scholar
Wilkinson, M. J., Wells, C. and Behnke, J. M. (1990). Necator americanus in the mouse: histopathological changes associated with the passage of larvae through the lungs of mice exposed to primary and secondary infection. Parasitology Research 76, 386–392.CrossRefGoogle ScholarPubMed
Williams-Blangero, S., Subedi, J., Upadhayay, R. P., Manral, D. B., Rai, D. R., Jha, B., Robinson, E. S. and Blangero, J. (1999). Genetic analysis of susceptibility to infection with Ascaris lumbricoides. The American Journal of Tropical Medical Hygiene 60, 921–926.CrossRefGoogle ScholarPubMed
Williams-Blangero, S., Vandeberg, J. L., Subedi, J., Aivaliotis, M. J., Rai, D. R., Upadhayay, R. P., Jha, B. and Blangero, J. (2002). Genes on chromosomes 1 and 13 have significant effects on Ascaris infection. Proceedings of the National Academy of Sciences, USA 99, 5533–5538.CrossRefGoogle ScholarPubMed
Wong, M. S., Bundy, D. A. and Golden, M. H. (1991). The rate of ingestion of Ascaris lumbricoides and Trichuris trichiura eggs in soil and its relationship to infection in two children's homes in Jamaica. Transactions of the Royal Society for Tropical Medicine and Hygiene 85, 89–91.CrossRefGoogle ScholarPubMed