Skip to main content
×
Home
    • Aa
    • Aa

Nutritional imbalances and infections affect the thymus: consequences on T-cell-mediated immune responses

  • Wilson Savino (a1) and Mireille Dardenne (a2)
Abstract

The thymus gland, where T lymphocyte development occurs, is targeted in malnutrition secondary to protein energy deficiency. There is a severe thymic atrophy, resulting from massive thymocyte apoptosis (particularly affecting the immature CD4+CD8+ cell subset) and decrease in cell proliferation. The thymic microenvironment (the non-lymphoid compartment that drives intrathymic T-cell development) is also affected in malnutrition: morphological changes in thymic epithelial cells were found, together with a decrease of thymic hormone production, as well as an increase of intrathymic contents of extracellular proteins. Profound changes in the thymus can also be seen in deficiencies of vitamins and trace elements. Taking Zn deficiency as an example, there is a substantial thymic atrophy. Importantly, marginal Zn deficiency in AIDS subjects, children with diarrhoea and elderly persons, significantly impairs the host's immunity, resulting in an increased risk of opportunistic infections and mortality; effects that are reversed by Zn supplementation. Thymic changes also occur in acute infectious diseases, including a severe thymic atrophy, mainly due to the depletion of CD4+CD8+ thymocytes, decrease in thymocyte proliferation, in parallel to densification of the epithelial network and increase in the extracellular matrix contents, with consequent disturbances in thymocyte migration and export. In conclusion, the thymus is targeted in several conditions of malnutrition as well as in acute infections. These changes are related to the impaired peripheral immune response seen in malnourished and infected individuals. Thus, strategies inducing thymus replenishment should be considered as adjuvant therapeutics to improve immunity in malnutrition and/or acute infectious diseases.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Nutritional imbalances and infections affect the thymus: consequences on T-cell-mediated immune responses
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Nutritional imbalances and infections affect the thymus: consequences on T-cell-mediated immune responses
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Nutritional imbalances and infections affect the thymus: consequences on T-cell-mediated immune responses
      Available formats
      ×
Copyright
Corresponding author
* Corresponding author: Wilson Savino, fax 55 21 38658101, email savino@fiocruz.br; w_savino@hotmail.com
References
Hide All
1.Chandra RK (1992) Protein-energy malnutrition and immunological responses. J Nutr 122, Suppl. 3, 597600.
2.Prentice AM (1999) The thymus: a barometer of malnutrition. Br J Nutr 81, 345347.
3.Savino W (2006) The thymus is a common target organ in infectious diseases. PLoS Pathogens 2, 472483.
4.Ciofani M & Zúñiga-Pflücker JC (2007) The thymus as an inductive site for T lymphopoiesis. Annu Rev Cell Dev Biol 23, 463493.
5.Savino W, Mendes da Cruz DA, Silva JS et al. (2002) Intrathymic T cell migration: a combinatorial interplay of extracellular matrix and chemokines? Trends Immunol 23, 305313.
6Savino W, Mendes-da-Cruz DA, Smaniotto S et al. . (2004) Control of thymocyte migration: an interplay of distinct cellular interactions. J Leukocyte Biol 75, 951961.
7.Savino W & Dardenne M (2000) Neuroendocrine control of thymus physiology. Endocr Rev 21, 412443.
8.Petrie HT & Züniga-Pflucker JC (2007) Zoned out: functional maing of stromal signaling microenvironments in the thymus. Annu Rev Immunol 25, 649679.
9.Mitsumori K, Takegawa K, Shimo T et al. . (1996) Morphometric and immunohistochemical studies on atrophic changes in lympho-hematopoietic organs of rats treated with piperonyl butoxide or subjected to dietary restriction. Arch Toxicol 70, 809814.
10.Lyra JS, Madi K, Maeda CT et al. . (1993) Thymic extracellular matrix in human malnutrition. J Pathol 171, 231236.
11Parent G, Chevalier P, Zalles L et al. . (1994) In vitro lymphocyte-differentiating effects of thymulin (Zn-FTS) on lymphocyte subpopulations of severely malnourished children. Am J Clin Nutr 60, 274278.
12.Aaby P, Marx C, Trautner S et al. . (2002) Thymus size at birth is associated with infant mortality: a community study from Guinea Bissau. Acta Pediatr 91, 698703.
13.Chevalier P, Sevilla R, Zalles L et al. . (1996) Immuno-nutritional recovery of children with severe malnutrition. Santé 6, 201208.
14.Kuvibidila S, Dardenne M, Savino W et al. . (1990) Influence of irondeficiency anemia on selected thymus functions in mice: thymulin biological activity, T-cell subsets, and thymocyte proliferation. Am J Clin Nutr 51, 228232.
15.Dhur A, Galan P, Christides JP et al. . (1991) Effect of folic acid deficiency upon lymphocyte subsets from lymphoid organs in mice. Comp Biochem Physiol A 98, 235240.
16.Malpuech-Brugere C, Nowacki W, Gueux E et al. . (1999) Accelerated thymus involution in magnesium-deficient rats is related to enhanced apoptosis and sensitivity to oxidative stress. Br J Nutr 81, 405411.
17.Nodera M, Yanagisawa H & Wada O (2001) Increased apoptosis in a variety of tissues of zinc-deficient rats. Life Sci 69, 16391649.
18.Cunningham-Rundles S, McNeeley DF & Moon A (2005) Mechanisms of nutrient modulation of the immune response. J Allergy Clin Immunol 115, 11191128.
19Shankar AH & Prasad AS (1998) Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr 68, 447S463S.
20.Chesters J (1977) Zinc. In Handbook of Nutritionally Essential Mineral Elements, pp. 185230 [Odel B Sunde R and EDS, editors]. New York: Marcel Dekker.
21.Fraker P, King L, Garvy B et al. (1993) Immunopathology of zinc deficiency: a role for apoptosis. In Human Nutrition: A Comprehensive Treatise, pp. 267283 [Klurfeld DM]. New York: Plenum Press.
22.Kuvibidila S, Yu L, Ode D et al. (1993) The immune response in protein-energy malnutrition and single nutrient deficiencies. In Human Nutrition: A Comprehensive Treatise, pp. 121157 [Klurfeld DM]. New York: Plenum Press.
23.Fraker P, King L, Laakko T et al. . (2000) The dynamic link between the integrity of the immune system and zinc status. J Nutr 130, 13991406.
24.Fernandes G, Nair N, Once K et al. . (1979) Impairment of cell mediated immunity function in dietary zinc deficiency in mice. Proc Natl Acad Sci USA 76, 457461.
25.Fraker PJ, Depascale-Jardieu R, Zwickl CM et al. . (1978) Regeneration of T-cell helper function in zinc-deficient adult mice. Proc Natl Acad Sci USA 75, 56605664.
26.King LE, Osati-Ashtiani F & Fraker PJ (2002) A distinct role for apoptosis in the loss of precursor lymphocytes during zinc deficiency. J Nutr 132, 974979.
27.Beach RS, Gershwin ME & Hurley LS (1979) Altered thymic structure and mitogen responsiveness in postnatally zinc-deprived mice. Dev Comp Immunol 3, 725738.
28.Fraker P, Osati-Ashtiani F, Wagner MA et al. . (1995) Possible roles for glucocorticoids and apoptosis in the suppression of lymphopoiesis during zinc deficiency: a review. J Am Coll Nutr 14, 1117.
29.Fraker PJ (2004) Roles for cell death in zinc deficiency. J Nutr 135, 359362.
30.Baum M, Shor-Posner G & Campa A (2000) Zinc status in human immunodeficiency virus infection. J Nutr 130, 1421S1423S.
31.Baum M, Campa A, Lai S, et al. . (2003) Zinc status in human immunodeficiency virus type 1 infection and illicit drug use. Clin Infect Dis 37, 117123.
32.Burguera JL, Burguera M, Alarcon OM et al. . (1988) Concentration changes of zinc, copper and iron in serum of chronic chagasic myocardiopathic patients. J Trace Elem Electrolytes Health Dis 2, 215219.
33.Matousek de Abel de la Cruz AJ, Burguera AJ, Burguera M et al. . (1993) Changes in total content of iron, copper and zinc in serum, heart, liver, spleen and skeletal muscle tissues of rats infected with Trypanosoma cruzi. Biol Trace Elem Res 37, 5170.
34.Fraker PJ, Caruso R & Kierszenbaum F (1982) Alteration of the immune and nutritional status of mice by synergy between zinc deficiency and infection with Trypanosoma cruzi. J Nutr 112, 12241229.
35.Leite-de-Moraes MC, Minoprio P, Dy M et al. . (1994) Endogenous IL-10 and IFN-g production controls thymic cell proliferation in mice acutely infected by Trypanosoma cruzi. Scand J Immunol 39, 5158.
36.Barone KS, O'Brien PC & Stevenson JR (1993) Characterization and mechanisms of thymic atrophy in protein-malnourished mice: role of corticosterone. Cell Immunol 148, 226233.
37.Munzberg H & Myers MG Jr.( 2005) Molecular and anatomical determinants of central leptin resistance. Nat Neurosci 8, 566570.
38.Lord GM, Matarese G, Howard JK et al. . (1998) Leptin modulates the T-cell immune response and reverses starvationinduced immunosuppression. Nature 394, 897901.
39.Farooqi IS, Matarese G, Lord GM et al. . (2002) Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 110, 10931103.
40.Howard JK, Lord GM, Matarese G et al. . (1999) Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice. J Clin Invest 104, 10511059.
41.Mito N, Yoshino H, Hosoda T et al. . (2004) Analysis of the effect of leptin on immune function in vivo using diet-induced obese mice. J Endocrinol 180, 167173.
42.Savino W (2002) The thymus gland is a target in malnutrition. Eur J Clin Nutr 56 (Suppl 3), S46S49.
43.Savino W, Dardenne M, Veloso LA et al. . (2007) The thymus is a common target in malnutrition and infection. Br J Nutr 98, 1116.
44.Leite de Moraes MC, Hontebeyrie-Joskowicz M, Leboulanger F et al. . (1991) Studies on the thymus in Chagas’ disease. II. Thymocyte subset fluctuations in Trypanosoma cruzi-infected mice: relationship to stress. Scand J Immunol 33, 267275.
45.Corrêa-de-Santana E, Paez-Pereda M, Theodoropoulou M et al. . (2006) Hypothalamus-pituitary-adrenal axis during Trypanosoma cruzi acute infection in mice. J Neuroimmunol 173, 1222.
46Perez AR, Bottasso O & Savino W (2009) The impact of infectious diseases upon neuroendocrine circuits. Neuroimmunomodulation 16, 96–105.
47.Cardenas-Palomo LF, de Souza-Matos DC, Chaves-Leal E et al. . (1995) Lymphocyte subsets and cell proliferation analysis in rabies-infected mice. J Clin Lab Immunol 46, 4961.
48.Roggero E, Pérez AR, Tamae-Kakazu M et al. . (2006) Endogenous glucocorticoids cause thymus atrophy but are protective during acute Trypanosoma cruzi infection. J Endocrinol 190, 495503.
49.Mittal A, Woodward B & Chandra RK (1988) Involution of thymic epithelium and low serum thymulin bioactivity in weanling mice subjected to severe food intake restriction or severe protein deficiency. Exp Mol Pathol 48, 226235.
50.Mittal A & Woodward B (1985) Thymic epithelial cells of severely undernourished mice: accumulation of cholesteryl esters and absence of cytoplasmic vacuoles. Proc Soc Exp Biol Med 178, 385391.
51.Savino W, Leite de Moraes MC, Hontebeyrie-Joskowicz M et al. . (1989) Studies on the thymus in Chagas’ disease. I. Changes in the thymic microenvironment in mice acutely infected with Trypanosoma cruzi. Eur J Immunol 19, 17271733.
52.Jambon B, Ziegler O, Maire B et al. . (1988) Thymulin (facteur thymique serique) and zinc contents of the thymus glands of malnourished children. Am J Clin Nutr 48, 335342.
53.Wade S, Bleiberg F, Mosse A et al. . (1985) Thymulin (Zn-facteur thymique serique) activity in anorexia nervosa patients. Am J Clin Nutr 42, 275280.
54Dardenne M, Savino W, Wade S et al. (1984) In vivo and in vitro studies of thymulin in marginally zinc-deficient mice. Eur J Immunol 14, 454458.
55.Prasad AS, Meftah S, Abdallah J et al. . (1988) Serum thymulin in human zinc deficiency. J Clin Invest 82, 12021210.
56.McDade TW, Beck MA, Kuzawa CW et al. . (2001) Prenatal undernutrition and postnatal growth are associated with adolescent thymic function. J Nutr 131, 12251231.
57.Dardenne M, Bach JF & Safai B (1983) Low serum thymic hormone levels in patients with acquired immunodeficiency syndrome. N Engl J Med 309, 4849.
58.Incefy GS, Pahwa S, Pahwa R et al. . (1986) Low circulating thymulin-like activity in children with AIDS and AIDS-related complex. AIDS Res 2, 109116.
59Savino W, Dardenne M, Marche C et al. . (1986) Thymic epithelium in AIDS: an immunohistologic study. Am J Pathol 122, 302307.
60.Cotta de Almeida V, Mendes da Cruz DA, Bonomo A et al. . (2003) Acute Trypanosoma cruzi infection modulates intrathymic contents of extracellular matrix ligands and receptors and alters thymocyte migration. Eur J Immunol 33, 24392448.
61.Mendes-da-Cruz DA, Silva JS, Cotta-de-Almeida V et al. . (2006) Altered thymocyte migration during experimental acute Trypanosoma cruzi infection: combined role of fibronectin and the chemokines CXCL12 and CCL4. Eur J Immunol 36, 14861493.
62.Savino W, Villa-Verde DMS, Mendes-da-Cruz DA et al. . (2007) Cytokines and cell adhesion receptors in the regulation of immunity to Trypanosoma cruzi. Cytokine Growth Factor Rev 18, 107124.
63.de Meis J, Morrot A, Farias-de-Oliveira DA et al. (2009) Differential regional immune response in Chagas disease. PLoS Negl Trop Dis 3, e417.
64.Andrade CF, Gameiro J, Nagib PR et al. . (2008) Thymic alterations in Plasmodium berghei-infected mice. Cell Immunol 253, 14.
65.Gameiro J, Nagib PRA, Andrade CF et al. . (2010) Changes in cell migration-related molecules expressed by thymic microenvironment during experimental Plasmodium berghei infection: consequences on thymocyte development. Immunology 129, 248256.
66Savino W, Dardenne M (2010) Pleiotropic modulation of thymic functions by growth hormone: from physiology to therapy. Curr Opinion Pharmacol 10, 434442.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Proceedings of the Nutrition Society
  • ISSN: 0029-6651
  • EISSN: 1475-2719
  • URL: /core/journals/proceedings-of-the-nutrition-society
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords:

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 12
Total number of PDF views: 96 *
Loading metrics...

Abstract views

Total abstract views: 212 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 22nd October 2017. This data will be updated every 24 hours.