Immune Mechanisms against Intracellular Pathogens

Abstract

Chronic infectious diseases in humans are caused by microorganisms that reside within phagocytes and epithelial cells. Host defence mechanisms against intracellular pathogens are primarily orchestrated by T lymphocytes via cytokine networks. Dysregulation of host responses lead to persistence of infection and immunopathology.

Keywords: immune response; intracellular pathogens; human pathogens; regulatory T cells; cytokines in infectious diseases

Figure 1.

DC‐SIGN of HIV favours infection of CD4 T cells: DC‐SIGN a C‐type lectin present on dendritic cell recongizes viral envelope glycoprotiens – gp 120. Immature DCs capture HIV at entry sites, achieve maturation and transmit the virus to CD4 T cells in the periphery. Low levels of HIV evades intracellular processes and degradation by entry through DC‐SIGN.

Figure 2.

Recognition/entry of Mycobacterium tuberculosis in dendritic cells is through diverse receptors: (a) It is targeted to the lysome by entry through mannose receptors, undergoes degradation and releases ManLAM. (b) Recogition by TLRs (Toll‐like receptors) results in activation of NF‐κB leading to immune activation. (c) DC‐SIGN binding high levels ManLAM results in immune suppression and deviation of intracellular killing. DC‐SIGN thus favours mycobacterial survivals whereas TLR aids in the host immune response.

Figure 3.

Cellular uptake of larger particles and pathogens (red bar) and of fluid or smaller particles (green dots). In phagocytosis the cell membrane is double and particles are trapped by circumferential pseudopods (convential). In coiling phagocytosis unilateral pseudopodia replicate and form tight whorls around the pathogen(s). In ‘loop’ phagocytosis irregular loop‐like pseudopods are put out by the host cell to capture the organism in a spacious phagosome. Whereas the phagosome tightly surrounds the organism in the former, in the ‘loop’ form it is spacious and looses around the organism. In macropinocytosis a single membrane fold bends towards the cell surface, trapping pericellular fluid.

Figure 4.

Role of accessory cells (monocytes (MO)/dendritic cells (DC)) in the differentiation of T‐helper cells: During the immune response/infection, accessory cells release diverse cytokines which lead to differentiation of specific subsets of Th cells, each with distinct function. Th1, Th2 are effector T cells whereas Th17 and Foxp3 have immune regulatory role of enhancing or suppressing immune responses respectively.

Figure 5.

Foxp3 T cells in the skin lesion of lepromatous leprosy patient detected by immunohistochemistry with specific mouse antihuman Foxp3 antibody and subsequently stained by horse‐radish peroxidase polymer (HRP Polymer) with Diamino benzamidine (DAB) as a substrate (original magnification X 200).

close

References

Banchereau J and Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392: 245–251.

Belkaid Y and Rouse BT (2005) Natural regulatory T cells in infectious disease. Nature Immunology 6: 353–360.

Berrebi D, Bruscoli S, Cohen N et al. (2003) Synthesis of glucocorticoid‐induced leucine zipper (GILZ) by macrophages: an anti‐inflammatory and immunosuppressive mechanism shared by glucocorticoids and IL 10. Blood 101: 729–738.

Betteli E, Oukka M and Kuchroo VK (2007) Th 17 cells in the circle of immunity and autoimmunity. Nature Immunology 8: 345–350.

Bi Y, Liu G and Yang R (2007) Th17 cell induction and immune regulatory effects. Journal of Cellular Physiology 211: 273–278.

Clemens DL, Lee Bai‐Yu and Horwitz MA (2005) Francisella tularensis enters macrophages via a novel process involving pseudopod loops. Infection and Immunity 73(9): 5892–5902.

Fearon DT and Locksley RM (1996) The instinctive role of innate immunity in the acquired immune response. Science 272: 50–53.

Hamdi H, Godot V, Maillot M et al. (2007) Induction of antigen specific regulatory T lymphocytes by human dendritic cells expressing the glucorticoid‐induced leucine zipper. Blood 110(1): 211–219.

Herkovits AA, Auerbuch V and Portnoy DA (2007) Bacterial ligands generated in a phagosome are targets of the cytosolic innate immune system. PLoS Pathogens 3(3): 431–443.

Horwitz DA, Zheng SG, Wang J and Gray JD (2008) The real role of TGF β in regulatory T cell physiology. (in Forum). European Journal of Immunology 38: 901–937.

Hui Pan, Bo‐Shlun Yan, Rojas M et al. (2005) Ipr1 gene mediates innate immunity to tuberculosis. Nature 434: 767–772.

Kaplan G, Mathur NK, Job CK, Nath I and Cohn ZA (1989) Effects of multiple interferon γ injections on the disposal of Mycobacterium leprae. Proceedings of the National Academy of Sciences of the USA 86: 8073–8077.

Linder S, Heimerl C, Fingerle V, Aepfelbacher M and Wilske B (2001) Coiling phagocytosis of Borrelia burgdorferi by primary human macrophages is controlled by CDC42Hs and Rac! And involves recruitment of Wiskott‐Aldrich Syndrome Protein and Arp2/3 complex. Infection and Immunity 69(3): 1739–1746.

Misra N, Murtaza A, Walker B et al. (1995) Cytokine profile of circulating T cells of leprosy patients reflect both indiscriminate and polarised Th subsets: Th phenotype is uninfluenced by related antigens of Mycobacterium leprae. Immunology 86: 97–103.

O'Garra A (1998) Cytokines induce the development of functionally heterogeneous T helper cell subsets. Immunity 8: 275–283.

Paul WE and Seder RA (1994) Lymphocyte responses and cytokines. Cell 76: 241–251.

Ridge JP, Di Rosa F and Matzinger P (1998) A conditioned dendritic cell can be a temporal bridge between a CD4+ T helper and a T‐killer cell. Nature 393: 474–477.

Sakaguchi S (2008) Regulatory T cells in the past and for the future in Viewpoints on T reg (in Forum). European Journal of Immunology 38: 901–937.

Sher A and Coffman RL (1992) Regulation of immunity to parasites by T cells and T cell derived cytokines. Annual Review of Immunology 10: 385–409.

Sirad J‐C, Vignal C, Dessein R and Chambillard M (2007) NOD‐like receptors: cytosolic watch dogs for immunity against pathogens. PLoS Pathogens 3(12): 1829–1836.

Sivasai KS, Prasad HK, Misra RS et al. (1993) Effect of recombinant interferon gamma administration on lesional monocytes/macrophages in lepromatous leprosy patients. International Journal of Leprosy and Other Mycobacterial Diseases 61(2): 259–269.

Sreenivasan P, Misra RS, Wilfred D and Nath I (1998) Lepromatous leprosy patients show T helper 1 like cytokine profile with differential expression of IL10 during type I and II reactions. Immunology 95: 529–536.

Sun J, Deghmane AE, Soualhine H et al. (2007) Mycobacterium bovis BCG disrupts the interaction of Rab7 with RILP contributing to inhibition of phagosome maturation. Journal of Leukocyte Biology 82: 1437–1445.

Tang Q and Bluestone JA (2008) The Foxp3+ regulatory T cell: a jack of all trades, master of regulation. Nature Immunology 9(3): 239–244.

Trinchieri G (1998) Interleukin 12: a cytokine at the interface of inflammation and infection. Advances in Immunology 70: 83–243.

van der Wel N, Hava D, Houben D et al. (2007) M. tuberculosis and M. leprae translocate from the phagolysosome to the cytosol in Myeloid cells. Cell 129: 1287–1298.

van Kooyk Y and Geijtenbeek BH (2003) DC‐SIGN: escape mechanism for pathogens. Nature Reviews 3: 697–709.

Further Reading

William E Paul (2003) Fundamental Immunology, 5th edn. Philadelphia: Lippin Cott‐Raven Publishers.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Nath, Indira(Dec 2008) Immune Mechanisms against Intracellular Pathogens. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000480.pub2]