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Infect Immun. 1992 September; 60(9): 3475-3479

The Th1/Th2-like switch in syphilitic infection: is it detrimental?

Department of Medical Microbiology and Immunology, School of Medicine, University of Minnesota, Duluth 55812.

ABSTRACT

Organisms that cause chronic diseases have evolved mechanisms to evade those immune defenses that resolve the acute stage of infection (10, 12-14, 21, 22, 32, 35, 37, 38, 40, 42, 45-49, 53). Much is to be learned by specifically identifying the mechanisms underlying these evasive strategies. Important new insights will emerge in terms of immunoregulatory pathways. This in turn will facilitate vaccine development. A good example is leishmania infection. The acute stage of this disease is resolved by DTH-macrophage activation. Leishmanial components preferentially activate Th2 lymphocytes. As a consequence, Th1 effects are minimized and infection is exacerbated leading to chronicity (10, 14, 32). To overcome this negative tendency, leishmanial vaccines are administered in combination with exogenous gamma interferon (42). This selects for Th1 predominance and generates protective immunity. Syphilis exhibits many parallels to the other nine chronic diseases mentioned above. Similarities include an acute localized stage that readily heals, early clearance via DTH-macrophage activation, transient concomitant immunity during acute infection, development of macrophage suppression through PGE2 down-regulation, beneficial effects of exogenous gamma interferon, and elements of autoimmunity. Some of the complexities of immunoregulation during treponemal infection have just begun to be unraveled. It will be important to develop further insight into the Th1/Th2 switch especially as it relates to chronicity. Macrophages seem to be intimately involved in the mechanics of this switch, and their specific role needs further clarification. Whatever is learned about syphilis, as well as other chronic infections will contribute to a better understanding of the generalized pathways of immunoregulation.

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