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Cytokine and chemokine factors

The significance of cytokine factor stem from the fact that the anti-chlamydial action of protective CD4 or CD8 Th1 cells appears to be dependent on the Th1 cytokines elaborated by these cells [Byrne et al., 1986; Holtmann et al., 1990; Igietseme et al., 2002; Loomis & Starnbach, 2002]. While Th1 cytokines that induce three anti-microbial processes [Igietseme et al., 1998] mediate protective immunity against chlamydia, there are indications the  induction of protective immunity would benefit from the absence of certain Th2 cytokines, such as IL-10. Thus, IL-10KO mice are highly resistance to both pulmonary and genital chlamydial infection [Igietseme et al., 1999; Igietseme et al., 2000; Yang et al., 1999] and IL-10KO APCs (including DC) are exceptionally effective at activating elevated levels of Th1 response in vitro, and are efficient cellular vaccines since they induced high frequency protective Th1 cells when antigen-pulsed DC are adoptively transferred into mice in vivo [Igietseme et al., 2000; see also Fig 3]. In addition, lymphocytes from chlamydial infected women with PID exhibited a significant reduction in IFN-γ production but elevated IL-10 secretion when exposed to chlamydial antigens in vitro [Cohen et al., 2000; de Battista et al., 2002]. Furthermore, an increase in IL-10 levels was detected in the endocerivcal secretions of women with non-ulcerative STDs, including chlamydia, which could enhance HIV-1 transmission [Cohen et al., 1999]. More so, clinical evidence has shown a high incidence of complications of chlamydial infection in individuals deficient of CD4 Th1 cells due to underlying HIV related AIDS [Cohen et al., 1999; Cohen et al., 2000; Kroon et al., 1989]. These findings would strong suggest that immunomodulatory strategies that will promote the required Th1 cytokines, such as IFN-γ, and limit the inhibitory Th2 cytokines (e.g. IL-10) should lead to the induction of protective immunity against chlamydia. However, adequate levels of the Th1 cytokines that will promote immunity without the inflammatory pathology will have to be established to achieve a safe chlamydial immunity. The induction of specific Th1-recruiting chemokines during primary and secondary genital chlamydial infection has been established [Belay et al., 2002; Darville et al., 2001a; Darville et al., 2001b; Maxion & Kelly, 2002],  while protective Th1 cells may be recruited to infected genital mucosa more efficiently under the influence of specific chemokines than non-protective Th2 cells  [Hawkins et al., 2002]. Although promising, the impact of conditionally expressed chemokines as an adjuvant system in a vaccine construct to modulate mucosal immune response against chlamydia is yet to be determined.