Hostname: page-component-586b7cd67f-2brh9 Total loading time: 0 Render date: 2024-11-24T03:24:29.879Z Has data issue: false hasContentIssue false
  • English
  • Français

Protein deficiency alters impact of intestinal nematode infection on intestinal, visceral and lymphoid organ histopathology in lactating mice

Published online by Cambridge University Press:  05 February 2014

LISA M. STARR ,
MAURICE R. ODIERE ,
KRISTINE G. KOSKI  and
MARILYN E. SCOTT
LISA M. STARR*
Affiliation:
Institute of Parasitology, McGill University (Macdonald Campus), Ste-Anne-de-Bellevue, Quebec, H9X 3V9, Canada
MAURICE R. ODIERE
Affiliation:
Institute of Parasitology, McGill University (Macdonald Campus), Ste-Anne-de-Bellevue, Quebec, H9X 3V9, Canada
KRISTINE G. KOSKI
Affiliation:
School of Dietetics and Human Nutrition, McGill University (Macdonald Campus), Ste-Anne-de-Bellevue, Quebec, H9X 3V9, Canada
MARILYN E. SCOTT
Affiliation:
Institute of Parasitology, McGill University (Macdonald Campus), Ste-Anne-de-Bellevue, Quebec, H9X 3V9, Canada
*
* Corresponding author: Institute of Parasitology, McGill University (Macdonald Campus), Ste-Anne-de-Bellevue, Quebec, H9X 3V9, Canada. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

Protein deficiency impairs local and systemic immune responses to Heligmosomoides bakeri infection but little is known about their individual and interactive impacts on tissue architecture of maternal lymphoid (thymus, spleen) and visceral (small intestine, kidney, liver, pancreas) organs during the demanding period of lactation. Using a 2×2 factorial design, pregnant CD1 mice were fed a 24% protein sufficient (PS) or a 6% protein deficient (PD) isoenergetic diet beginning on day 14 of pregnancy and were infected with 100 H. bakeri larvae four times or exposed to four sham infections. On day 20 of lactation, maternal organs were examined histologically and serum analytes were assayed as indicators of organ function. The absence of villus atrophy in response to infection was associated with increased crypt depth and infiltration of mast cells and eosinophils but only in lactating dams fed adequate protein. Infection-induced lobular liver inflammation was reduced in PD dams, however, abnormalities in the kidney caused by protein deficiency were absent in infected dams. Bilirubin and creatinine were highest in PD infected mice. Infection-induced splenomegaly was not due to an increase in the lymphoid compartment of the spleen. During lactation, infection and protein deficiency have interactive effects on extra-intestinal pathologies.

Keywords

Heligmosomoides bakeriprotein deficiencyextra-intestinal histopathologylactationnematodetrickle infectionliverspleenkidneyduodenum
Type
Research Article
Information
Parasitology , Volume 141 , Issue 6 , May 2014 , pp. 801 - 813
Check for updates
Copyright
Copyright © Cambridge University Press 2014 

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

REFERENCES

Ali, N. M. and Behnke, J. M. (1985). Observations on gross changes in the secondary lymphoid organs of mice infected with Nematospiroides dubius . Journal of Helminthology 59, 167–174.CrossRefGoogle ScholarPubMed
Artis, D. and Grencis, R. K. (2008). The intestinal epithelium: sensors to effectors in nematode infection. Mucosal Immunology 1, 252–264.CrossRefGoogle ScholarPubMed
Banner, B. F., Savas, L., Zivny, J., Tortorelli, K. and Bonkovsky, H. L. (2000). Ubiquitin as a marker of cell injury in nonalcoholic steatohepatitis. American Journal of Clinical Pathology 114, 860–866.CrossRefGoogle ScholarPubMed
Barone, K. S., O'Brien, P. C. and Stevenson, J. R. (1993). Characterization and mechanisms of thymic atrophy in protein-malnourished mice: role of corticosterone. Cellular Immunology 148, 226–233.CrossRefGoogle ScholarPubMed
Barrio Rendo, M. E. (1995). Depressed response of the erythropoietin-responsive splenic cell population to erythropoietin in acutely protein restricted mice. In Vivo 9, 71–73.Google ScholarPubMed
Baumler, M. D., Koopmann, M. C., Thomas, D. D., Ney, D. M. and Groblewski, G. E. (2010). Intravenous or luminal amino acids are insufficient to maintain pancreatic growth and digestive enzyme expression in the absence of intact dietary protein. American Journal of Physiology – Gastrointestinal and Liver Physiology 299, G338–G347.CrossRefGoogle ScholarPubMed
Behnke, J. M., Lowe, A., Clifford, S. and Wakelin, D. (2003). Cellular and serological responses in resistant and susceptible mice exposed to repeated infection with Heligmosomoides polygyrus bakeri . Parasite Immunology 25, 333–340.CrossRefGoogle ScholarPubMed
Bell, R. G., Hazell, L. A. and Price, P. (1976). Influence of dietary protein restriction on immune competence II. Effect on lymphoid tissue. Clinical and Experimental Immunology 26, 314–326.Google ScholarPubMed
Boulay, M., Scott, M. E., Conly, S. L., Stevenson, M. M. and Koski, K. G. (1998). Dietary protein and zinc restrictions independently modify a Heligmosomoides polygyrus (Nematoda) infection in mice. Parasitology 116, 449–462.CrossRefGoogle ScholarPubMed
Brailsford, T. J. and Behnke, J. M. (1992). The dynamics of trickle infections with Heligmosomoides polygyrus in syngeneic strains of mice. International Journal for Parasitology 22, 351–359.CrossRefGoogle ScholarPubMed
Brannon, P. M. (1990). Adaptation of the exocrine pancreas to diet. Annual Review of Nutrition 10, 85–105.CrossRefGoogle ScholarPubMed
Cable, J., Harris, P. D., Lewis, J. W. and Behnke, J. M. (2006). Molecular evidence that Heligmosomoides polygyrus from laboratory mice and wood mice are separate species. Parasitology 133, 111–122.CrossRefGoogle ScholarPubMed
Camargo, J. L., Angeleli, A. Y., Burini, R. C. and Campana, A. O. (1978). Hepatic lesions in protein-deficient adult rats. British Journal of Experimental Pathology 59, 158–166.Google ScholarPubMed
Casirola, D. M. and Ferraris, R. P. (2003). Role of the small intestine in postpartum weight retention in mice. American Journal of Clinical Nutrition 78, 1178–1187.CrossRefGoogle ScholarPubMed
CCAC (1993). Guide to the Care and Use of Experimental Animals. Canadian Council on Animal Care, Ottawa, Canada.Google Scholar
Cliffe, L. J., Humphreys, N. E., Lane, T. E., Potten, C. S., Booth, C. and Grencis, R. K. (2005). Accelerated intestinal epithelial cell turnover: a new mechanism of parasite expulsion. Science 308, 1463–1465.CrossRefGoogle ScholarPubMed
Coop, R. L. and Kyriazakis, I. (1999). Nutrition–parasite interaction. Veterinary Parasitology 84, 187–204.CrossRefGoogle ScholarPubMed
Cooper, P. (2009). Mucosal immunology of geohelminth infections in humans. Mucosal Immunology 2, 288–299.CrossRefGoogle ScholarPubMed
Corbin, E., Vicente, J., Martin-Hernando, M. P., Acevedo, P., Pérez-Rodriguez, L. and Gortazar, C. (2008). Spleen mass as a measure of immune strength in mammals. Mammal Review 38, 108–115.CrossRefGoogle Scholar
Coutinho, E. M., De Souza, M. M., Silva, L. M., Cavalcanti, C. L., De Araujo, R. E., Barbosa, A. A. Jr., Cheever, A. W. and Andrade, Z. A. (1997). Pathogenesis of schistosomal ‘pipestem’ fibrosis: a low-protein diet inhibits the development of ‘pipestem’ fibrosis in mice. International Journal of Experimental Pathology 78, 337–342.CrossRefGoogle ScholarPubMed
Crandall, R. B., Crandall, C. A. and Franco, J. A. (1974). Heligmosomoides polygyrus (=Nematospiroides dubius): humoral and intestinal immunologic responses to infection in mice. Experimental Parasitology 35, 275–287.CrossRefGoogle ScholarPubMed
Crispe, I. N., Dao, T., Klugewitz, K., Mehal, W. Z. and Metz, D. P. (2000). The liver as a site of T-cell apoptosis: graveyard, or killing field? Immunological Reviews 174, 47–62.CrossRefGoogle ScholarPubMed
Cywińska, A., Czumińska, K. and Schollenberger, A. (2004). Granulomatous inflammation during Heligmosomoides polygyrus primary infections in FVB mice. Journal of Helminthology 78, 17–24.CrossRefGoogle ScholarPubMed
Ezernitchi, A. V., Vaknin, I., Cohen-Daniel, L., Levy, O., Manaster, E., Halabi, A., Pikarsky, E., Shapira, L. and Baniyash, M. (2006). TCR ζ down-regulation under chronic inflammation is mediated by myeloid suppressor cells differentially distributed between various lymphatic organs. Journal of Immunology 177, 4763–4772.CrossRefGoogle ScholarPubMed
Finney, C. A., Taylor, M. D., Wilson, M. S. and Maizels, R. M. (2007). Expansion and activation of CD4+CD25+ regulatory T cells in Heligmosomoides polygyrus infection. European Journal of Immunology 37, 1874–1886.CrossRefGoogle ScholarPubMed
Gause, W. C., Urban, J. F. Jr. and Stadecker, M. J. (2003). The immune response to parasitic helminths: insights from murine models. Trends in Immunology 24, 269–277.CrossRefGoogle ScholarPubMed
Graber, S. E. and Krantz, S. B. (1978). Erythropoietin and the control of red cell production. Annual Review of Medicine 29, 51–66.CrossRefGoogle ScholarPubMed
Hammond, K. A. (1997). Adaptation of the maternal intestine during lactation. Journal of Mammary Gland Biology and Neoplasia 2, 243–252.CrossRefGoogle ScholarPubMed
Hashimoto, K., Uchikawa, R., Tegoshi, T., Takeda, K., Yamada, M. and Arizono, N. (2009). Depleted intestinal goblet cells and severe pathological changes in SCID mice infected with Heligmosomoides polygyrus . Parasite Immunology 31, 457–465.CrossRefGoogle ScholarPubMed
Hou, C., Gheorghiu, S., Huxley, V. H. and Pfeifer, P. (2010). Reverse engineering of oxygen transport in the lung: adaptation to changing demands and resources through the space-filling networks. PLoS Computational Biology 6, e1000902.CrossRefGoogle ScholarPubMed
Ing, R., Su, Z., Scott, M. E. and Koski, K. G. (2000). Suppressed T helper 2 immunity and prolonged survival of a nematode parasite in protein-malnourished mice. Proceedings of the National Academy of Sciences USA 97, 7078–7083.CrossRefGoogle ScholarPubMed
Jiao, Y.-F., Okumiya, T., Saibara, T., Kudo, Y. and Sugiura, T. (2001). Erythrocyte creatine as a marker of excessive erythrocyte destruction due to hypersplenism in patients with liver cirrhosis. Clinical Biochemistry 34, 395–398.CrossRefGoogle ScholarPubMed
Jones, L. A., Houdijk, J. G., Sakkas, P., Bruce, A. D., Mitchell, M., Knox, D. P. and Kyriazakis, I. (2011). Dissecting the impact of protein versus energy host nutrition on the expression of immunity to gastrointestinal parasites during lactation. International Journal for Parasitology 41, 711–719.CrossRefGoogle ScholarPubMed
Jones, L. A., Sakkas, P., Houdijk, J. G., Knox, D. P. and Kyriazakis, I. (2012). Amelioration of the periparturient relaxation of immunity to parasites through a reduction in mammalian reproductive effort. International Journal for Parasitology 42, 1127–1134.CrossRefGoogle ScholarPubMed
Kamal, M., Dehlawi, M. S., Rosa Brunet, L. and Wakelin, D. (2002). Paneth and intermediate cell hyperplasia induced in mice by helminth infections. Parasitology 125, 275–281.CrossRefGoogle ScholarPubMed
Kittel, B., Ruehl-Fehlert, C., Morawietz, G., Klapwijk, J., Elwell, M. R., Lenz, B., O'Sullivan, M. G., Roth, D. R. and Wadsworth, P. F. (2004). Revised guides for organ sampling and trimming in rats and mice – Part 2. Experimental and Toxicologic Pathology 55, 413–431.CrossRefGoogle ScholarPubMed
Klahr, S. and Alleyne, G. A. (1973). Effects of chronic protein-calorie malnutrition on the kidney. Kidney International 3, 129–141.CrossRefGoogle ScholarPubMed
Kristan, D. M. (2002). Effects of intestinal nematodes during lactation: consequences for host morphology, physiology and offspring mass. Journal of Experimental Biology 205, 3955–3965.CrossRefGoogle ScholarPubMed
Kristan, D. M. and Hammond, K. A. (2004). Morphological plasticity varies with duration of infection: evidence from lactating and virgin wild-derived house mice (Mus musculus) infected with an intestinal parasite (Heligmosomoides polygyrus; Nematoda). Journal of Experimental Biology 207, 2351–2360.CrossRefGoogle ScholarPubMed
Kyriazakis, I. and Houdijk, J. (2006). Immunonutrition: nutritional control of parasites. Small Ruminant Research 62, 79–82.CrossRefGoogle Scholar
Liu, S.-K. (1965). Pathology of Nematospiroides dubius. I. Primary infections in C3H and Webster mice. Experimental Parasitology 17, 123–135.CrossRefGoogle ScholarPubMed
Madden, K. B., Whitman, L., Sullivan, C., Gause, W. C., Urban, J. F. Jr., Katona, I. M., Finkelman, F. D. and Shea-Donohue, T. (2002). Role of STAT6 and mast cells in IL-4- and IL-13-induced alterations in murine intestinal epithelial cell function. Journal of Immunology 169, 4417–4422.CrossRefGoogle ScholarPubMed
Manhart, N., Vierlinger, K., Bergmeister, H., Boltz-Nitulescu, G., Spittler, A. and Roth, E. (2000). Influence of short-term protein malnutrition of mice on the phenotype and costimulatory signals of lymphocytes from spleen and Peyer's patches. Nutrition 16, 197–201.CrossRefGoogle ScholarPubMed
McDermott, J. R., Humphreys, N. E., Forman, S. P., Donaldson, D. D. and Grencis, R. K. (2005). Intraepithelial NK cell-derived IL-13 induces intestinal pathology associated with nematode infection. Journal of Immunology 175, 3207–3213.CrossRefGoogle ScholarPubMed
Mittal, A., Woodward, B. and Chandra, R. K. (1988). Involution of thymic epithelium and low serum thymulin bioactivity in weanling mice subjected to severe food intake restriction or severe protein deficiency. Experimental and Molecular Pathology 48, 226–235.CrossRefGoogle ScholarPubMed
Moeser, A. J., Nighot, P. K., Ryan, K. A., Wooten, J. G. and Blikslager, A. T. (2006). Prostaglandin-mediated inhibition of Na+/H+ exchanger isoform 2 stimulates recovery of barrier function in ischemia-injured intestine. American Journal of Physiology – Gastrointestinal and Liver Physiology 291, G885–G894.CrossRefGoogle ScholarPubMed
Mohrs, K., Harris, D. P., Lund, F. E. and Mohrs, M. (2005). Systemic dissemination and persistence of Th2 and type 2 cells in response to infection with a strictly enteric nematode parasite. Journal of Immunology 175, 5306–5313.CrossRefGoogle ScholarPubMed
Morawietz, G., Ruehl-Fehlert, C., Kittel, B., Bube, A., Keane, K., Halm, S., Heuser, A. and Hellmann, J. (2004). Revised guides for organ sampling and trimming in rats and mice – Part 3. Experimental and Toxicologic Pathology 55, 433–449.CrossRefGoogle ScholarPubMed
NRC (1995). Nutrient Requirements of Laboratory Animals, 4th Edn. National Research Council, National Academy of Sciences, Washington, DC, USA.Google Scholar
Odiere, M. R., Koski, K. G., Weiler, H. A. and Scott, M. E. (2010 a). Concurrent nematode infection and pregnancy induce physiological responses that impair linear growth in the murine foetus. Parasitology 137, 991–1002.CrossRefGoogle ScholarPubMed
Odiere, M. R., Scott, M. E., Weiler, H. A. and Koski, K. G. (2010 b). Protein deficiency and nematode infection during pregnancy and lactation reduce maternal bone mineralization and neonatal linear growth in mice. Journal of Nutrition 140, 1638–1645.CrossRefGoogle ScholarPubMed
Odiere, M. R., Scott, M. E., Leroux, L.-P., Dzierszinski, F. S. and Koski, K. G. (2013). Maternal protein deficiency during a gastrointestinal nematode infection alters developmental profile of lymphocyte populations and selected cytokines in neonatal mice. Journal of Nutrition 143, 100–107.CrossRefGoogle ScholarPubMed
Parker, S. J. and Inchley, C. J. (1990). Early lymphocytic responses to Heligmosomoides polygyrus infections in mice. Journal of Helminthology 64, 35–45.CrossRefGoogle ScholarPubMed
Pond, W. G., Ellis, K. J., Mersmann, H. J., Heath, J. P., Krook, L. P., Burrin, D. G., Dudley, M. A. and Sheng, H.-P. (1996). Severe protein deficiency and repletion alter body and brain composition and organ weights in infant pigs. Journal of Nutrition 126, 290–302.CrossRefGoogle ScholarPubMed
Pritchard, D. I., Williams, D. J., Behnke, J. M. and Lee, T. G. (1983). The role of IgG1 hypergammaglobulinaemia in immunity to the gastrointestinal nematode Nematospiroides dubius. The immunochemical purification, antigen-specificity and in vivo anti-parasite effect of IgG1 from immune serum. Immunology 49, 353–365.Google Scholar
Reynolds, L. A., Filbey, K. J. and Maizels, R. M. (2012). Immunity to the model intestinal helminth parasite Heligmosomoides polygyrus . Seminars in Immunopathology 34, 829–846.CrossRefGoogle Scholar
Ruehl-Fehlert, C., Kittel, B., Morawietz, G., Deslex, P., Keenan, C., Mahrt, C. R., Nolte, T., Robinson, M., Stuart, B. P. and Deschl, U. (2003). Revised guides for organ sampling and trimming in rats and mice – Part 1. Experimental and Toxicologic Pathology 55, 91–106.CrossRefGoogle ScholarPubMed
Samuel, I., Toriumi, Y., Yokoo, H., Wilcockson, D. P., Trout, J. J. and Joehl, R. J. (1994). Ligation-induced acute pancreatitis in rats and opossums: a comparative morphologic study of the early phase. Journal of Surgical Research 57, 299–311.CrossRefGoogle ScholarPubMed
Scott, M. E. (1990). An experimental and theoretical study of the dynamics of a mouse-nematode (Heligmosomoides polygyrus) interaction. Parasitology 101, 75–92.CrossRefGoogle ScholarPubMed
Shea-Donohue, T., Sullivan, C., Finkelman, F. D., Madden, K. B., Morris, S. C., Goldhill, J., Piñeiro-Carrero, V. and Urban, J. F. Jr. (2001). The role of IL-4 in Heligmosomoides polygyrus-induced alterations in murine intestinal epithelial cell function. Journal of Immunology 167, 2234–2239.CrossRefGoogle ScholarPubMed
Stadnyk, A. W. and Gauldie, J. (1991). The acute phase protein response during parasitic infection. Immunology Today 12, A7–A12.CrossRefGoogle ScholarPubMed
Stear, M. J., Bishop, S. C., Doligalska, M., Duncan, J. L., Holmes, P. H., Irvine, J., McCririe, L., McKellar, Q. A., Sinski, E. and Murray, M. A. (1995). Regulation of egg production, worm burden, worm length and worm fecundity by host responses in sheep infected with Ostertagia circumcincta . Parasite Immunology 17, 643–652.CrossRefGoogle ScholarPubMed
Stogdale, L. (1981). Correlation of changes in blood chemistry with pathological changes in the animal's body: II electrolytes, kidney function tests, serum enzymes, and liver function tests. Journal of the South African Veterinary Association 52, 155–164.Google ScholarPubMed
Su, Z. and Dobson, C. (1997). Genetic and immunological adaptation of Heligmosomoides polygyrus in mice. International Journal for Parasitology 27, 653–663.CrossRefGoogle ScholarPubMed
Su, Z., Segura, M., Morgan, K., Loredo-Osti, J. C. and Stevenson, M. M. (2005). Impairment of protective immunity to blood-stage malaria by concurrent nematode infection. Infection and Immunity 73, 3531–3539.CrossRefGoogle ScholarPubMed
Sukhdeo, M. V. and Mettrick, D. F. (1984). Heligmosomoides polygyrus (syn. Nematospiroides dubius) (Nematoda): distribution and net fluxes of glucose, H2O, Na+, K+, and Cl− in the mouse small intestine. Canadian Journal of Zoology 62, 37–40.CrossRefGoogle Scholar
Tan, J. K. and O'Neill, H. C. (2010). Investigation of murine spleen as a niche for hematopoiesis. Transplantation 89, 140–145.CrossRefGoogle ScholarPubMed
Tetsutani, K., Ishiwata, K., Ishida, H., Tu, L., Torii, M., Hamano, S., Himeno, K. and Hisaeda, H. (2009). Concurrent infection with Heligmosomoides polygyrus suppresses anti-Plasmodium yoelii protection partially by induction of CD4+ CD25+ Foxp3+ Treg in mice. European Journal of Immunology 39, 2822–2830.CrossRefGoogle ScholarPubMed
Tu, T., Koski, K. G. and Scott, M. E. (2007). Mechanisms underlying reduced expulsion of a murine nematode infection during protein deficiency. Parasitology 135, 81–93.CrossRefGoogle ScholarPubMed
Umar, S. (2010). Intestinal stem cells. Current Gastroenterology Reports 12, 340–348.CrossRefGoogle ScholarPubMed
Urban, J. F. Jr., Katona, I. M. and Finkelman, F. (1991). Heligmosomoides polygyrus: CD4+ but not CD8+ T cells regulate the IgE response and protective immunity in mice. Experimental Parasitology 73, 500–511.CrossRefGoogle Scholar
Vallance, B. A. and Collins, S. M. (1998). The effect of nematode infection upon intestinal smooth muscle function. Parasite Immunology 20, 249–253.CrossRefGoogle ScholarPubMed
Zhang, L., Lizzio, E. F., Chen, T. and Kozlowski, S. (2005). Peptide immunization excludes antigen−specific T cells from splenic lymphoid compartments. European Journal of Immunology 35, 776–785.CrossRefGoogle ScholarPubMed