Interactions of malnutrition and immune impairment, with specific reference to immunity against parasites

S Hughes, P Kelly, S Hughes, P Kelly

Abstract

1. Clinical malnutrition is a heterogenous group of disorders including macronutrient deficiencies leading to body cell mass depletion and micronutrient deficiencies, and these often coexist with infectious and inflammatory processes and environmental problems. 2. There is good evidence that specific micronutrients influence immunity, particularly zinc and vitamin A. Iron may have both beneficial and deleterious effects depending on circumstances. 3. There is surprisingly slender good evidence that immunity to parasites is dependent on macronutrient intake or body composition.

Figures

Figure 1
Figure 1
Evidence of depletion of dendritic cell (DC) number s and dysfunction of DCs in the child whose case is described in the text. A and B FACS (fluorescence activated cell sorter) plot of peripheral blood mononuclear cells (PBMCs) after initial selection by side scatter and CD45 expression. Each point represents one PBMC, and the intensity of staining with lineage markers (CD3, CD14, CD16, CD19, CD56) is shown on the x axis. DCs have little or no staining for these markers. HLA-DR staining is shown on the y axis; DCs have high DR staining and the box therefore includes those cells tha are likely DCs. A FACS plot on admission; B just prior to discharge, after good nutritional recovery and DC numbers have increased from 0·32% to 0·84% of PBMCs. C and D histograms of cultured DCs at rest (blue shading) and after stimulation with lipopolysaccharide (open histogram delineated by black line) which is expected to stimulate DCs; isotype control is shown as green histogram. C cells from admission sample fail to upregulate HLA-DR, but D after nutritional recovery the capacity to upregulate HLA-DR is restored.

References

    1. Amadi B, Mwiya M, Chomba E, et al. Improved nutritional recovery on an elemental diet in Zambian children with persistent diarrhoea and malnutrition. J Trop Paediatr. 2005;51:5–10.
    1. Hviid L. Naturally acquired immunity to Plasmodium falciparum malaria in Africa. Acta Trop. 2005;95:270–275.
    1. Kelly P, Jack D, Naeem A, et al. Mannose Binding Lectin is a contributor to mucosal defence against Cryptosporidium parvum in AIDS Patients. Gastroenterology. 2000;119:1236–1242.
    1. Garred P, Nielsen MA, Kurtzhals JA, et al. Mannose-binding lectin is a disease modifier in clinical malaria and may function as opsonin for Plasmodium falciparum-infected erythrocytes. Infect Immun. 2003;71:5245–5253.
    1. Kane CM, Cervi L, Sun J, et al. Helminth antigens modulate TLR-initiated dendritic cell activation. J Immunol. 2004;173:7454–7461.
    1. Coban C, Ishii KJ, Kawai T, et al. Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin. J Exp Med. 2005;201:19–25.
    1. Chen X-M, O’Hara SP, Nelson JB, et al. Multiple TLRs are expressed in human cholangiocytes and mediate host epithelial defense responses to Cryptosporidium parvum via activation of NF-κB. J Immunol. 2005;175:7447–7456.
    1. Sacks D, Sher A. Evasion of innate immunity by parasitic protozoa. Nat Immunol. 2002;3:1041–1047.
    1. Janeway CA. The road less travelled by: the role of innate immunity in the adaptive immune response. J Immunol. 1998;161:539–544.
    1. McDonald V. Host cell-mediated responses to infection with Cryptosporidium. Parasite Immunol. 2000;22:597–604.
    1. Golla JA, Larson LA, Anderson CF, Lucas AR, Wilson WR, Tomasi TB. An immunological assessment of patients with anorexia nervosa. Am J Clin Nutr. 1981;34:2756–2762.
    1. Bessler H, Karp L, Notti I, et al. Cytokine production in anorexia nervosa. Clin Neuropharmacol. 1993;16:237–243.
    1. Allende LM, Corell A, Manzanares J, et al. Immunodeficiency associated with anorexia nervosa is secondary and improves after refeeding. Immunology. 1998;94:543–551.
    1. Martinsen TC, Bergh K, Waldum HL. Gastric juice: a barrier against infectious diseases. Basic Clin Pharmacol Toxicol. 2005;96:84–102.
    1. Macallan DC. Nutrition and immune function in HIV infection. Proc Nutr Soc. 1999;58:743–748.
    1. Zulu I, Veitch A, Sianongo S, et al. Albendazole chemotherapy for AIDS-related diarrhoea in Zambia – clinical, parasitological and mucosal responses. Aliment Pharmacol Ther. 2002;16:595–601.
    1. Melchior JC, Gelas P, Carbonnel F, et al. Improved survival by home total parenteral nutrition in AIDS patients: follow up of a randomized controlled trial. Nutrition. 1997;13:272.
    1. Purtilo DT, Connor DH. Fatal infections in protein-calorie malnourished children with thymolymphatic atrophy. Arch Dis Child. 1975;50:149–152.
    1. Hughes WT, Price RA, Sisko F, et al. Protein-calorie malnutrition. A host determinant for Pneumocystis carinii infection. Am J Dis Child. 1974;128:44–52.
    1. Shimeles D, Lulseged S. Clinical profile and pattern of infection in Ethiopian children with severe protein-energy malnutrition. East Afr Med J. 1994;71:264–267.
    1. Zaman K, Baqui AH, Yunus M, Sack RB, Chowdhury HR, Black RE. Malnutrition cell-mediated immune deficiency and acute upper respiratory infections in rural Bangladeshi children. Acta Paediatr. 1997;86:923–927.
    1. Lindtjorn B, Alemu T, Bjorvatn B. Nutritional status and risk of infection among Ethiopian children. J Trop Paediatr. 1993;39:76–82.
    1. Caulfield LE, Richard SA, Black RE. Undernutrition as an underlying cause of malaria morbidity and mortality in children less than 5 years old. Am J Trop Med Hyg. 2004;71(Suppl. 2):55–63.
    1. Murray MJ, Murray AB, Murray NJ, Murray MB. Diet and cerebral malaria: the effect of famine and refeeding. Am J Clin Nutr. 1978;31:57–61.
    1. Badaro R, Jones TC, Carvalho EM, et al. New perspectives on a subclincial form of visceral leishmaniasis. J Infect Dis. 1986;154:1003–1011.
    1. Smythe PM, Brereton-Stiles GG, Grace HJ, et al. Thymolymphatic deficiency and depression of cell-mediated immunity in protein-calorie malnutrition. Lancet. 1971;2:939–943.
    1. Parent G, Chevalier P, Zalles L, et al. In vitro lymphocyte-differentiating effects of thymulin (Zn-FTS) on lymphocyte subpopulations of severely malnourished children. Am J Clin Nutr. 1994;60:274–278.
    1. McMurray DN, Loomis SA, Casazza LJ, Rey H, Miranda R. Development of impaired cell-mediated immunity in mild and moderate malnutrition. Am J Clin Nutr. 1981;34:68–77.
    1. Rosen EU, Geefhuysen J, Anderson R, Joffe M, Rabson AR. Leucocyte function in children with kwashiorkor. Arch Dis Child. 1975;50:220–224.
    1. Fakhir S, Ahmad P, Faridi MA, Rattan A. Cell-mediated immune responses in malnourished host. J Trop Paediatr. 1989;35:175–178.
    1. Lotfy OA, Saleh WA, el-Barbari M. A study of some changes of cell-mediated immunity in protein energy malnutrition. J Egypt Soc Parasitol. 1998;28:413–428.
    1. Chandra RK. 1990 McCollum Award lecture. Nutrition and immunity: lessons from the past and new insights into the future. Am J Clin Nutr. 1991;53:1087–1101.
    1. Ozkan H, Olgun M, Sasmaz E, Abacioglu H, Okuyan M, Cevik N. Nutrition immunity and infections: T lymphocyte subpopulations in protein-energy malnutrition. J Trop Paediatr. 1993;39:257–260.
    1. Najera O, Gonzalez C, Toledo G, Lopez L, Ortiz R. Flow cytometry study of lymphocyte subsets in malnourished children and well-nourished children with bacterial infections. Clin Diagn Lab Immunol. 2004;11:577–580.
    1. Suskind R, Sirishinha S, Vithayasai V, et al. Immunoglobulins and antibody response in children with protein-calorie malnutrition. Am J Clin Nutr. 1976;29:836–841.
    1. Moore SE, Goldblatt D, Bates CJ, Prentice AM. Impact of nutritional status on antibody responses to different vaccines in undernourished Gambian children. Acta Paediatr. 2003;92:170–176.
    1. Chandra RK, Newberne PM. Nutrition Immunity and Infection: Mechanisms of Interactions. New York: Plenum Press; 1977.
    1. Reddy V, Raghuramulu N, Bhaskaram C. Secretory IgA in protein-calorie malnutrition. Arch Dis Child. 1976;51:871–874.
    1. Beatty DW, Napier B, Sinclair-Smith CC, McCabe K, Hughes EJ. Secretory IgA synthesis in Kwashiorkor. J Clin Lab Immunol. 1983;12:31–36.
    1. Doherty JF, Golden MH, Raynes JG, Griffin GE, McAdam KP. Acute-phase protein response is impaired in severely malnourished children. Clin Sci (Lond) 1993;84:169–175.
    1. Morlese JF, Forrester T, Jahoor F. Acute-phase protein response to infection in severe malnutrition. Am J Physiol. 1998;275:E112–E117.
    1. Reid M, Badaloo A, Forrester T, Morlese JF, Heird WC, Jahoor F. The acute-phase protein response to infection in edematous and nonedematous protein-energy malnutrition. Am J Clin Nutr. 2002;76:1409–1415.
    1. Sirisinha S, Edelman R, Suskind R, Charupatana C, Olson RE. Complement and C3-proactivator levels in children with protein-calorie malnutrition and effect of dietary treatment. Lancet. 1973;1:1016–1020.
    1. Selvaraj RJ, Bhat KS. Metabolic and bactericidal activities of leucocytes in protein-calorie malnutrition. Am J Clin Nutr. 1972;25:166–174.
    1. Vasquez-Garibay E, Campollo-Rivas O, Romero-Velarde E, et al. Effect of renutrition on natural and cell-mediated immune response in infants with severe malnutrition. J Paediatr Gastroenterol Nutr. 2002;34:296–301.
    1. Seth V, Chandra RK. Opsonic activity phagocytosis and bactericidal capacity of polymorphs in undernutrition. Arch Dis Child. 1972;47:282–284.
    1. Nayak KC, Sethi AS, Aggarwal TD, Chadda VS, Kumar KK. Bactericidal power of neutrophils in protein calorie malnutrition. Indian J Paediatr. 1989;56:371–377.
    1. Munoz C, Arevalo M, Lopez M, Schlesinger L. Impaired interleukin-1 and tumour necrosis factor production in protein-calorie malnutrition. Nutr Res. 1994;14:347–352.
    1. Bhaskaram P, Sivakumar B. Interleukin-1 in malnutrition. Arch Dis Child. 1986;61:182–185.
    1. Harland PSEG. Tuberculin reactions in malnourished children. Lancet. 1965;2:719–721.
    1. Satyanarayana K, Bhaskaram P, Seshu VC, Reddy V. Influence of nutrition on postvaccinial tuberculin sensitivity. Am J Clin Nutr. 1980;33:2334–2337.
    1. Ortiz R, Campos C, Gomez JL, Espinoza M, Ramos-Motilla M, Betancourt M. Effect of renutrition on the proliferation kinetics of PHA stimulated lymphocytes from malnourished children. Mutat Res. 1995;334:235–241.
    1. Chevalier P, Sevilla R, Sejas E, Zalles L, Belmonte G, Parent G. Immune recovery of malnourished children takes longer than nutritional recovery: implications for treatment and discharge. J Trop Paediatr. 1998;44:304–307.
    1. Watson RR, McMurray DN, Martin P, Reyes MA. Effect of age, malnutrition and renutrition on free secretory component and IgA in secretions. Am J Clin Nutr. 1985;42:281–288.
    1. Siekmann JH, Allen LH, Watnik MR, et al. Titers of antibody to common pathogens: relation to food-based interventions in rural Kenyan schoolchildren. Am J Clin Nutr. 2003;77:242–249.
    1. Pichard C, Sudre P, Karsegard V, et al. A randomized double-blind controlled study of 6 months of oral nutritional supplementation with arginine and omega-3 fatty acids in HIV-infected patients. Swiss HIV Cohort Study. AIDS. 1998;12:53–63.
    1. Singer P, Levine R, Rothkopf M, Askanazi J. Home parenteral lipids in AIDS: a three-month study. Nutrition. 1997;13:104–109.
    1. Faggioni R, Feingold KR, Grunfeld C. Leptin regulation of the immune response and the immunodeficiency of malnutrition. FASEB J. 2001;15:2565–2571.
    1. Howard JK, Lord GM, Matarese G, et al. Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice. J Clin Invest. 1999;104:1051–1059.
    1. Semba RD. Vitamin A and immunity to viral, bacterial and protozoan infections. Proc Nutr Soc. 1999;58:719–727.
    1. Binka FN, Ross DA, Morris SS, et al. Vitamin A supplementation and childhood malaria in northern Ghana. Am J Clin Nutr. 1995;61:853–859.
    1. Shankar AH, Genton B, Semba RD, et al. Effect of vitamin A supplementation on morbidity due to Plasmodium falciparum in young children in Papua New Guinea: a randomised controlled trial. Lancet. 1999;354:203–209.
    1. Cox SE, Staalsoe T, Arthur P, et al. Maternal Vitamin A supplementation and immunity to malaria in pregnancy in Ghanaian primigravids. Trop Med Int Health. 2005;10:1286–1297.
    1. Stephensen CB. Vitamin A, infection and immune function. Annu Rev Nutr. 2001;21:167–192.
    1. Stephensen CB, Rasooly R, Jian X, et al. Vitamin A enhances in vitro Th2 development via retinoid X receptor pathway. J Immunol. 2002;168:4495–4503.
    1. Ma Y, Chen Q, Ross AC. Retinoic acid and polyriboinosinic: polyribocytidylic acid stimulate robust anti-tetanus antibody production while differentially regulating type 1/type 2 cytokines and lymphocyte populations. J Immunol. 2005;174:7961–7969.
    1. Villamor E, Fawzi WW. Effects of vitamin a supplementation on immune responses and correlation with clinical outcomes. Clin Microbiol Rev. 2005;18:446–464.
    1. Filteau SM, Rollins NC, Coutsoudis A, Sullivan KR, Willumsen JF, Tomkins AM. The effect of antenatal vitamin A and beta-carotene supplementation on gut integrity of infants of HIV-infected South African women. J Paediatr Gastroenterol Nutr. 2001;32:464–470.
    1. Fawzi WW, Msamanga GI, Spiegelman D, et al. A randomized trial of multivitamin supplements and HIV disease progression and mortality. New Engl J Med. 2004;351:23–32.
    1. Black RE. Zinc deficiency, infectious disease and mortality in the developing world. J Nutr. 2003;133:1485S–1489S.
    1. Bhutta ZA and the Zinc Investigators’ Collaborative Group. Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials. Am J Clin Nutr. 2000;72:1516–1522.
    1. Doherty CP, Sarkar MA, Shakur MS, Ling SC, Elton RA, Cutting WA. Zinc and rehabilitation from severe protein-energy malnutrition: higher-dose regimens are associated with increased mortality. Am J Clin Nutr. 1998;68:742–748.
    1. Muller O, Becher H, van Zweeden AB, et al. Effect of zinc supplementation on malaria and other causes of morbidity in west African children: randomised double blind placebo controlled trial. BMJ. 2001;322:1567–1570.
    1. Anonymous. Zinc therapy of depressed cellular immunity in acrodermatitis enteropathica. Nutr Rev. 1981;39:168–170.
    1. Sazawal S, Jalla S, Mazumder S, Sinha A, Black RE, Bhan MK. Effect of zinc supplementation on cell-mediated immunity and lymphocyte subsets in preschool children. Indian Paediatr. 1997;34:589–597.
    1. Bohane TD, Cutz E, Hamilton JR, Gall DG. Acrodermatitis enteropathica, zinc, and the Paneth cell. A case report with family studies. Gastroenterology. 1977;73:587–592.
    1. Kelly P, Feakins R, Domizio P, et al. Paneth cell granule depletion in the human small intestine under infective and nutritional stress. Clin Exp Immunol. 2004;135:303–309.
    1. Fraker PJ, King LE, Laakko T, Vollmer TL. The dynamic link between the integrity of the immune system and zinc status. J Nutr. 2000;130:1399S–1406S.
    1. Fraker PJ, Caruso R, Kierszenbaum F. Alteration of the immune and nutritional status of mice by synergy between zinc deficiency and infection with Trypanosoma cruzi. J Nutr. 1982;112:1224–1229.
    1. Cook-Mills JM, Wirth JJ, Fraker PJ. Possible roles for zinc in destruction of Trypanosoma cruzi by toxic oxygen metabolites produced by mononuclear phagocytes. Adv Exp Med Biol. 1990;262:111–121.
    1. Arif AJ, Mathur PD, Chandra S, Singh C, Sen AB. Effect of zinc diet on xanthine oxidase activity of liver in mice infected with Plasmodium berghei. Indian J Malariol. 1987;24:59–63.
    1. Rink L, Kirchner H. Zinc-altered immune function and cytokine production. J Nutr. 2000;130:1470S–1411S.
    1. Cousins RJ. A role of zinc in the regulation of gene expression. Proc Nutr Soc. 1998;57:307–311.
    1. Prasad AS. Effects of zinc deficiency on Th1 and Th2 cytokine shifts. J Infect Dis. 2000;182(Suppl. 1):S62–S68.
    1. Oppenheimer SJ. Iron and it relation to immunity and infectious disease. J Nutr. 2001;131:616S–635S.
    1. Bullen JJ, Rogers HJ, Leigh L. Iron binding proteins in milk and resistance to Escherichia coli infection in infants. Br Med J. 1972;1:69–75.
    1. Murray MJ, Murray A, Murray CJ. The salutary effect of milk on amoebiasis and its reversal by iron. Be Med J. 1980;1:1351–1352.
    1. Murray MJ, Murray AB, Murray MB, Murray CJ. The adverse effect of iron repletion on the course of certain infections. BMJ. 1978;2:1113–1115.
    1. Nyakeriga AM, Trove-Blomberg M, Dorfman JR, et al. Iron deficiency and malaria among children living on the coast of Kenya. J Infect Dis. 2004;190:439–447.
    1. Doherty CP, Weaver LT, Prentice AM. Micronutrient supplementation and infection: a double-edged sword? J Paediatr Gastroenterol Nutr. 2002;34:346–352.
    1. Sazawal S, Black RE, Ramsan M, et al. Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised placebo-controlled trial. Lancet. 2006;367:133–143.
    1. Arthur JR, McKenzie RC, Beckett GJ. Selenium in the immune system. J Nutr. 2003;133:1457S–1459S.
    1. Roy M, Kiremidjian-Schumacher L, Wishe HI, Cohen MW, Stotzky G. Supplementation with selenium and human immune cell functions. I. Effect on lymphocyte proliferation and interleukin 2 receptor expression. Biol Trace Elem Res. 1994;41:103–114.
    1. Kiremidjian-Schumacher L, Roy M, Wishe HI, Cohen MW, Stotzky G. Supplementation with selenium and human immune cell functions. II. Effect on cycotoxic lymphocytes and natural killer cells. Biol Trace Elem Res. 1994;41:115–127.
    1. Broome CS, McArdle F, Kyle JAM, et al. An increase in selenium intake imprioves immune function and poliovirus handling in adults with marginal selenium statrus. Am J Clin Nutr. 2004;80:154–162.
    1. Meydani SN, Maydani M, Blumberg JB, et al. Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized controlled trial. JAMA. 1997;277:1380–1386.

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