Abstract
Protective immunity to intracellular bacteria such as mycobacteria and salmonellae depends on an effective cell-mediated immune response (CMI). A major effector mechanism of CMI is the activation of infected macrophages by type-1 cytokines, particularly interferon-gamma (IFN-y). IFN-y is produced by natural killer (NK) and T helper-1 (Thl) cells and its production is regulated by interleukin-12 (IL-12) and interleukin-18 (IL-18), both of which are released by activated macrophages and dendritic cells (Fig. 1) [Ottenhoff and Mutis, 1995; Kumararatne et al., 1990]. IFN-y together with monokines such as TNF-a, activates microbicidal mechanisms of macrophages that are thought to be responsible for the control and elimination of the intracellular infectious pathogen. Moreover, IFN-y induces and enhances MHC class I and II expression, and modulates expression of other molecules involved in antigen presentation, such as proteasomes and TAP, thus resulting in increased immune T cell activation. Patients are likely to benefit from supplementary IFN-y therapy and in the case of IL-12 deficiency, IL-12 supplementation may be an option as well. As a prophylactic measure, live bacterial vaccines such as M. bovis BCG and typhoid vaccines, as well as live viral vaccines, such as yellow fever, should preferably be avoided. Exposure to infectious diseases, such as tuberculosis, listeriosis, salmonellosis and leishmaniasis should obviously be minimized, given the increased risk to develop severe infections. Genetic correction strategies may be developed in the nearby future, including transplantation with gene transduced autologous stem cells.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Altare, F., Durandy, A., Lammas, D., Emile, J., et al., 1998, Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. Science 280: 1432–1435
Altare, F., Lammas, D., Revy, P., Jouanguy, E., et al., 1998, Inherited interleukin-12 deficiency in a child with Bacille Calmette-Guerin and Salmonella enteritidis disseminated infection. J. Clin. Invest. 102: 2035–2040.
Altare, F., Youanguy, E., Lamhamedi-Cherradi, S., Fondaneche, M.C., et al., 1998, A causative relationship between mutant IFN-?R1 alleles and impaired cellular response to IFN-y in a compound heterozygous child. Am. Hum. Genet. 62: 723–726.
Bloom, B.R., and Godal, T., 1983, Selective primary health care: strategies for control of disease in the developing world. V. Leprosy. Rev. Infect. Dis. 5:765–780.
Casanova, J.-L., Jouanguy, E., Lamhamedi,S., Blanche, S., and Fischer, A., 1995, Immunological conditions of children with BCG disseminated infection. Lancet 346: 581.
Casanova, J.-L., Blanche, S., Emile, J.F., Jouanguy, E., et al., 1996, Idiopathic disseminated bacillus Calmette-Guérin infection: a French national retrospective study. Pediatrics 98: 774–778.
De Vries, R.R.P., and Ottenhoff T.H.M.,1994, Immunogenetics of Leprosy. In Leprosy (R.C. Hastings. ed), Churchill Livingstone, New York, pp 113–123.
Döffinger, R., Jouanguy, E., Dupuis, S., Fondan¨¨che, M-C., et al., 2000, Partial interferon-(receptor signaling chain deficiency in a patient with Bacille Calmette-Guérin and Mycobacterium abscessus infection. J. Infect. Dis. 181: 379–384.
Döffinger R, Smahi A, Bessia C, Geissmann F, et al., 2001, X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling. Nat Genet. 27: 277–285
Dorman, S.E., and Holland, S.M., 1998, Mutation in the signal-transducing chain of the interferon-(receptor and susceptibility to mycobacterial infection. J. Clin. Invest. 101: 2364–2369.
Dorman, S.E., Uzel, G., Roesler, J., Bradley, J.S., et al., 1999,Viral infections in interferon-gamma receptor deficiency. J.Pediatr. 135: 640–643.
Emile, J.F., Patey, N., Altare, F., Lamhamedi, S., Jouanguy, E., Boman, F., Quillard, J., Lecomte-Houcke, M., Verola, O., Mousnier, J.F., Dijoud, F., Blanche, S., Fischer, A., Brousse, N., Casanova, J-L., 1997, Correlation of granuloma structure with clinical outcome defines two types of idiopathic disseminated BCG infections. J. Pathol. 181: 25–30.
Frucht, D.M., and Holland, S.M., 1996, Defective monocyte costimulation for IFN-y production in familial disseminated Mycobacterium avium complex infection: abnormal IL-12 regulation. J. Immunol. 157: 411–416.
Haraguchi, S., Day, N., Nelson, R.J., Emmanuel, P., et al., 1998, Interleukin-12 deficiency associated with recurrent infections. Proc. Natl. Acad. Sci. USA 95: 13125–13129.
Holland, S.M., Dorman, S.E., Kwon, A., Pitha-Rowe, et al., 1998, Abnormal regulation of interferon gamma, interleukin 12, and tumor necrosis factor-alpha in interferon-gamma receptor 1 deficiency. J. Infect. Dis. 178: 1095–1104.
De Jong, R. D., Altare, F., Haagen, I., Elferink, D. G., et al., 1998, Severe mycobacterial and Salmonella infections in interleukin-12 receptor deficient patients. Science 280: 1435–1438.
Jouanguy, E., Altare, F., Lamhamedi-Cherradi, S., Casanova, J.L., 1997, Infections in IFNGR-1-deficient children. J Interf. Cyt. Res. 17: 583–587.
Jouanguy, E., Lamhamedi-Cherradi, S., Altare, F., Fondanche, M.C., et al., 1997, Partial Interferon-(Receptor 1 Deficiency in a Child with Tuberculoid Bacillus Calmette-Guérin Infection and a Sibling with Clinical Tuberculosis. J. Clin. Invest. 100: 2658–2664
Jouanguy, E., Lamhamedi-Cherradi, S., Lammas, D., Dorman, S.E., et al., 1999, A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection. Nature Gen. 21, 370–378.
Kohno, K., Kataoka, J., Ohtsuki, T., Suemoto, Y., et al., 1997, IFN-gamma-inducing factor (IGIF) is a costimulatory factor on the activation of Th1 but not Th2 cells and exerts its effect independently of IL-12. J. Immunol. 158: 1541–1550.
Kumararatne, D.S., Pithie, A.S., Drysdale, P., Gaston, J.S., et al., 1990, Specific lysis of mycobacterial antigen-bearing macrophages by class II MHC-restricted polyclonal T cell lines in healthy donors or patients with tuberculosis. Clin. Exp. Immunol. 80, 314–323.
Levin, M., Newport, M., D’Souza, S., Kalabalibis, P., et al., 1995, disseminated atypical mycobacterial infection in childhood: a human mycobacterial susceptibility gene? Lancet 345: 79–83.
Newport, M.J., Huxley, C., Huston, S., Hawrylowicz, C.M., et al., 1996, A mutation in the interferon-(receptor gene and susceptibility to mycobacterial infection. N. Engl. J. Med. 335: 1941–1949.
Novelli, F., Bernabei, P., Ozmen, L., Rigamonti, L., et al., 1996, Switching on of the proliferation or apoptosis of activated human T lymphocytes by IFN-y is correlated with the differential expression of the V- and 3-chains of its receptor. J. Immunol.157: 1935–1943.
Ottenhoff, T.H.M. and Mutis, T., 1995, Role of cytotoxic cells in the protective immunity against and immunopathology of intracellular infections. Eur. J. Clin. Invest. 25: 371–377.
Ottenhoff, T.H.M., Kumararatne, D. and Casanova, J.L., 1998, Novel immuno-deficiencies reveal the essential role of type 1 cytokines in immunity to tracellular bacteria. Immunol. Today 19: 491–494.
Pierre-Audigier, C., Jouanguy, E., Lamhamedi, S., Altare, F., Rauzier, J., Vincent, V., Canioni, D., Emile, J.F., Fischer, A., Blanche, S., Gaillard, J.L., Casanova, J.L., 1997, Fatal disseminated Mycobacterium smegmatis infection in a child with inherited interferon-gamma receptor deficiency. Clin. Infect. Dis. 24: 982–984.
Robinson, D., Shibuya, K., Mui, A., Zonin, F., et al., 1997, IGIF does not drive Thl development but synergizes with IL-12 for interferon-gamma production and activates IRAK and NFkappaB. Immunity 7: 571–581.
Rogge, L., Barberis-Maino, L., Biffi, M., Passini, M., et al., 1997, Selective expression of an interleukin-12 receptor component by human T helper 1 cells. J. Exp. Med. 185: 825–831.
Roesler, J., Kofink, B., Wendisch, J., Heyden, S., et al., 1999, Listeria mono-cytogenes and recurrent mycobacterial infections in a child with complete interferon-gamma-receptor (IFNgammaRl) deficiency: mutational analysis and evaluation of therapeutic options. Exp. Hematol. 27: 1368–1374.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer Science+Business Media New York
About this chapter
Cite this chapter
Ottenhoff, T.H.M., De Boer, T., van Dissel, J.T., Verreck, F.A.W. (2003). Human Deficiencies in Type-1 Cytokine Receptors Reveal the Essential Role of Type-1 Cytokines in Immunity to Intracellular Bacteria. In: Marzuki, S., Verhoef, J., Snippe, H. (eds) Tropical Diseases. Advances in Experimental Medicine and Biology, vol 531. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0059-9_24
Download citation
DOI: https://doi.org/10.1007/978-1-4615-0059-9_24
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-4905-1
Online ISBN: 978-1-4615-0059-9
eBook Packages: Springer Book Archive