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

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.

The pattern and level of cytokines secreted by Th1 and Th2 lymphocytes of syphilitic patients correlate to the progression of the disease

“…The result of this report indicated additionally that Th2 lymphocytes are able to produce cytokines early in the disease, when Th1 lymphocytes weakly produce cytokines and in early latent syphilis in which for many years syphilis remains latent. Fitzgerald [38] hypothesized that Th1 response is dominant in primary syphilis and then shifts to Th2 as the disease progresses to the secondary stage. The results of our work seem to indicate that such shift to Th2, which acts as a negative feedback mechanism to control and limit T cell activation, could occur in early latent syphilis when only IL-12 (not published) and IL-10 are secreted.…”

Cytokine gene expression in skin of susceptible guinea‐pig infected with Treponema pallidum

“…8 In the guinea‐pig model, a predominant Th2 immune response was observed as early as 3 days after infection. In the rabbit model, Fitzgerald 26 reported a switch from a Th1 [IL‐2, interferon‐γ (IFN‐γ)] to a Th2 response after 9–14 days of infection. Van Voorhis et al ., 27 using skin biopsies obtained from African patients with primary and secondary syphilis, suggested that the predominantly Th1 response (IL‐2, IL‐12 and IFN‐γ) seen in patients with primary syphilis must be responsible for the effective clearance of the pathogen from the site of infection and dissolution of lesions.…”

Persistent Infection and Long-Term Carriage of Typhoidal and Nontyphoidal Salmonellae

“…Different studies have suggested that chronic infection with various bacterial, viral, and parasitic agents involves a cytokine switch from a Th1 to a Th2 immune response (234)(235)(236)(237). Although this model might represent an oversimplification of the immune response (238), the establishment of persistence can be schematically described as two distinct phases, characterized by a different balance of Th1/Th2 responses (Fig.…”