Hypothesis implications for vaccine development
C. trachomatis is a relatively ubiquitous sexually transmitted
pathogen with a predilection to establish persistent infection,
and host defenses in the female genital tract likely evolved in the
constant presence of this bacterium. To optimize the opportunities
for survival and transmission, C. trachomatis also evolved to elicit
responses that suppress, but do not disarm, host defense. It is quite
possible, therefore, that both the character and strength of the im-
mune responses elicited against other sexually transmitted patho-
gens have been adjusted by evolution to counter the diminution of
genital tract inﬂammatory responses that is sequelae to persistent
Chlamydia infection. If our hypothesis is correct, and C. trachomatis
stimulates polarization toward T
2 immunity and alternative mac-
rophage activation, then a prophylactic chlamydial vaccine admin-
istered to women prior to sexual debut has the potential to height
en reactivity to other sexually transmitted microorganisms, and, in
some individuals, increase the possibility for immunopathological
genital tract damage. Much less speculative, development of
vaccines that induce strong Chlamydia-speciﬁc T
1 memory would
similarly increase the probability for collateral tissue damage upon
repetitive exposure to C. trachomatis in the female genital tract.
Therefore, as ectopic pregnancy and tubal factor infertility are less
frequent consequences of C. trachomatis infection in areas of the
world that maintain chlamydial infection control programs,
development of vaccines that suppress phenotypic expression of
disease, versus vaccines that stimulate Chlamydia-speciﬁc T
memory, may warrant greater emphasis. Even more likely,
however, is the possibility that vaccines eliciting appropriate Chla-
2-stimulated humoral immune responses will re-
duce incident C. trachomatis infection in the female genital tract.
Though implications of our hypothesis are plausible or thought
provoking, the more basic and immediate objective should be the
elucidation of the speciﬁc effector CD4
T cell subsets induced by
genital tract C. trachomatis infection, as this is prerequisite for
deﬁning the optimal approach to Chlamydia vaccine development.
Conﬂict of interest statement
Authors have no ﬁnancial and personal relationships with other
people or organizations to disclose that inappropriately inﬂuenced
This work was supported by the Department of Pediatrics
(University of Pittsburgh School of Medicine) and the National
Institutes of Health (grant R01HD072663). Authors declare
sponsors had no role in the collection, analysis and interpretation
of data; in the writing of the manuscript; and in the decision to
submit the manuscript for publication.
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4 R.D. Vicetti Miguel, T.L. Cherpes / Medical Hypotheses xxx (2012) xxx–xxx
Please cite this article in press as: Vicetti Miguel RD, Cherpes TL. Hypothesis: Chlamydia trachomatis infection of the female genital tract is controlled by
Type 2 immunity. Med Hypotheses (2012), http://dx.doi.org/10.1016/j.mehy.2012.07.032