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

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 r...

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Main Authors: Lewis, R., Behnke, Jerzy M., Cassidy, J.P., Stafford, P., Murray, N., Holland, Celia V.
Format: Article
Published: Cambridge University Press 2007
Subjects:
Online Access:https://eprints.nottingham.ac.uk/29415/
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author Lewis, R.
Behnke, Jerzy M.
Cassidy, J.P.
Stafford, P.
Murray, N.
Holland, Celia V.
author_facet Lewis, R.
Behnke, Jerzy M.
Cassidy, J.P.
Stafford, P.
Murray, N.
Holland, Celia V.
author_sort Lewis, R.
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-294152020-05-04T20:28:18Z https://eprints.nottingham.ac.uk/29415/ The migration of Ascaris suum larvae, and the associated pulmonary inflammatory response in susceptible C57BL/6j and resistant CBA/Ca mice Lewis, R. Behnke, Jerzy M. Cassidy, J.P. Stafford, P. Murray, N. Holland, Celia V. 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. Cambridge University Press 2007-08 Article PeerReviewed Lewis, R., Behnke, Jerzy M., Cassidy, J.P., Stafford, P., Murray, N. and Holland, Celia V. (2007) The migration of Ascaris suum larvae, and the associated pulmonary inflammatory response in susceptible C57BL/6j and resistant CBA/Ca mice. Parasitology, 134 (9). pp. 1301-1314. ISSN 0031-1820 Ascaris suum mouse model immune response bronchoalveolar lavage C57BL/6j CBA/Ca susceptibility lungs migration http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=1217828&fileId=S0031182007002582 doi:10.1017/S0031182007002582 doi:10.1017/S0031182007002582
spellingShingle Ascaris suum
mouse model
immune response
bronchoalveolar lavage
C57BL/6j
CBA/Ca
susceptibility
lungs
migration
Lewis, R.
Behnke, Jerzy M.
Cassidy, J.P.
Stafford, P.
Murray, N.
Holland, Celia V.
The migration of Ascaris suum larvae, and the associated pulmonary inflammatory response in susceptible C57BL/6j and resistant CBA/Ca mice
title The migration of Ascaris suum larvae, and the associated pulmonary inflammatory response in susceptible C57BL/6j and resistant CBA/Ca mice
title_full The migration of Ascaris suum larvae, and the associated pulmonary inflammatory response in susceptible C57BL/6j and resistant CBA/Ca mice
title_fullStr The migration of Ascaris suum larvae, and the associated pulmonary inflammatory response in susceptible C57BL/6j and resistant CBA/Ca mice
title_full_unstemmed The migration of Ascaris suum larvae, and the associated pulmonary inflammatory response in susceptible C57BL/6j and resistant CBA/Ca mice
title_short The migration of Ascaris suum larvae, and the associated pulmonary inflammatory response in susceptible C57BL/6j and resistant CBA/Ca mice
title_sort migration of ascaris suum larvae, and the associated pulmonary inflammatory response in susceptible c57bl/6j and resistant cba/ca mice
topic Ascaris suum
mouse model
immune response
bronchoalveolar lavage
C57BL/6j
CBA/Ca
susceptibility
lungs
migration
url https://eprints.nottingham.ac.uk/29415/
https://eprints.nottingham.ac.uk/29415/
https://eprints.nottingham.ac.uk/29415/