Article

Hypothesis: Chlamydia trachomatis infection of the female genital tract is controlled by Type 2 immunity

University of Pittsburgh School of Medicine, Department of Pediatrics, Rangos Research Center, 4401 Penn Avenue Pittsburgh, PA 15224, USA.
Medical Hypotheses (Impact Factor: 1.07). 09/2012; 79(6). DOI: 10.1016/j.mehy.2012.07.032
Source: PubMed
ABSTRACT
Chlamydia trachomatis is an obligate intracellular bacterium sexually transmitted to more than 90 million individuals each year. As this level of infectivity implies, C. trachomatis is a successful human parasite; a success facilitated by its ability to cause asymptomatic infection. Host defense against C. trachomatis in the female genital tract is not well defined, but current dogma suggests infection is controlled largely by T(H)1 immunity. Conversely, it is well established that T(H)2 immunity controls allergens, helminths, and other extracellular pathogens that cause repetitive or persistent T cell stimulation but do not induce the exuberant inflammation that drives T(H)1 and T(H)17 immunity. As C. trachomatis persists in female genital tract epithelial cells but does not elicit over tissue inflammation, we now posit that defense is maintained by Type 2 immune responses that control bacterial growth but minimize immunopathological damage to vital reproductive tract anatomy. Evaluation of this hypothesis may uncover novel mechanisms by which Type 2 immunity can control growth of C. trachomatis and other intracellular pathogens, while confirmation that T(H)2 immunity was selected by evolution to control C. trachomatis infection in the female genital tract will transform current research, now focused on developing vaccines that elicit strong, and therefore potentially tissue destructive, Chlamydia-specific T(H)1 immunity.

Full-text

Available from: Thomas Cherpes, Apr 30, 2014
Hypothesis: Chlamydia trachomatis infection of the female genital tract is
controlled by Type 2 immunity
Rodolfo D. Vicetti Miguel, Thomas L. Cherpes
University of Pittsburgh School of Medicine, Department of Pediatrics, Rangos Research Center, 4401 Penn Avenue Pittsburgh, PA 15224, USA
article info
Article history:
Received 29 April 2012
Accepted 29 July 2012
Available online xxxx
abstract
Chlamydia trachomatis is an obligate intracellular bacterium sexually transmitted to more than 90 million
individuals each year. As this level of infectivity implies, C. trachomatis is a successful human parasite; a
success facilitated by its ability to cause asymptomatic infection. Host defense against C. trachomatis in
the female genital tract is not well defined, but current dogma suggests infection is controlled largely
by T
H
1 immunity. Conversely, it is well established that T
H
2 immunity controls allergens, helminths,
and other extracellular pathogens that cause repetitive or persistent T cell stimulation but do not induce
the exuberant inflammation that drives T
H
1 and T
H
17 immunity. As C. trachomatis persists in female gen-
ital tract epithelial cells but does not elicit over tissue inflammation, we now posit that defense is main-
tained by Type 2 immune responses that control bacterial growth but minimize immunopathological
damage to vital reproductive tract anatomy. Evaluation of this hypothesis may uncover novel mecha-
nisms by which Type 2 immunity can control growth of C. trachomatis and other intracellular pathogens,
while confirmation that T
H
2 immunity was selected by evolution to control C. trachomatis infection in the
female genital tract will transform current research, now focused on developing vaccines that elicit
strong, and therefore potentially tissue destructive, Chlamydia-specific T
H
1 immunity.
Ó 2012 Elsevier Ltd. All rights reserved.
Introduction
Host defense
Protection against microbial pathogens is orchestrated by a coor-
dinated system in which innate immune responses supply the first
lines of defense and drive the formation of more specialized adaptive
immune responses. Depending on the infection, dendritic cells (DC)
and other innate immune cells express distinct sets of co-stimulatory
molecules and cytokines that trigger naïve CD4
+
T cells to form vari-
ous types of effector cells, three of which are termed T
H
1, T
H
2, and
T
H
17 [1]. Specifically, many intracellular bacteria and viruses induce
DC and natural killer (NK) cells to produce interleukin (IL)-12 and
interferon (IFN)-
c
, which drivesT
H
1differentiation; helminths and
other extracellular pathogens cause innate immune cells to secrete
IL-4, which promotes T
H
2 differentiation; while other bacteria and
fungi stimulate DC to produceIL-1, IL-6, and transforming growthfac-
tor-b, which induces T
H
17 differentiation [2–5].Suchspecialized
adaptive immune responses allow animal hosts to optimize their de-
fenses against the diverse array of naturally encountered pathogens.
Naïve CD4
+
T cells, stimulated to formT
H
1 cells, secrete high lev-
els of IFN-
c
, activating macrophages (called classical macrophage
activation) to phagocytose and eliminate the microbes that trig-
gered T
H
1 development [6].T
H
1 CD4
+
T cells also secrete tumor
necrosis factor and proinflammatory chemokines that recruit addi-
tional leukocytes to active infection sites [7]. However, when T
H
1
immunity cannot adequately control infection, host defense may
be polarized toward Type 2 immune responses that curb T
H
1-med-
iated inflammation and inhibit collateral tissue damage [8]. For
example, helminths and other extracellular pathogens refractory
to phagocytic killing stimulate T
H
2 CD4
+
T cells to secrete IL-4,
and IL-13, responses that inhibit T
H
1 and T
H
17 cell development,
decrease inflammatory cell recruitment, and activate macrophages
to promote tissue remodeling and wound healing (called alterna-
tive macrophage activation) [9,10].
Endocervical Chlamydia trachomatis infection
Chlamydia trachomatis is an obligate intracellular bacterium,
and exclusively a pathogen of humans. With at least 90 million
new cases globally each year, this microorganism is the most com-
mon sexually transmitted bacterium [11]. The highest prevalences
of genital tract Chlamydia infection are found among adolescents
and young adults, and migration of the organism from the lower
to upper female genital tract can cause Fallopian tube damage
and increase the risk for ectopic pregnancy and tubal factor
infertility [12]. Persistent infection is another risk factor for
phenotypic expression of chlamydial disease [13], and is facilitated
0306-9877/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.mehy.2012.07.032
Corresponding author. Address: Room 9123, Rangos Research Center, 4401
Penn Avenue, Pittsburgh, PA 15224, USA. Tel.: +1 412 692 3599; fax: +1 412 692
5565.
E-mail address: cherpestl@upmc.edu (T.L. Cherpes).
Medical Hypotheses xxx (2012) xxx–xxx
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Medical Hypotheses
journal homepage: www.elsevier.com/locate/mehy
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
Page 1
by the ability of C. trachomatis to asymptomatically infect women
[14]. In fact, without administration of an appropriate antimicro-
bial, this organism can persist subclinically in genital tract epithe-
lium for years after initial infection [15]. Interestingly, chlamydial
infection control programs that augment detection and treatment
of asymptomatically individuals concomitantly increase popula-
tional susceptibility to infection, suggesting that an earlier eradica-
tion of the organism interrupts development of slow-to-form
Chlamydia-specific protective immunity [16–18]. Moreover, even
though C. trachomatis is a Gram-negative bacterium, its cell wall
contains lipopolysaccharide (LPS) that is at least 100-fold less po-
tent than LPS contained in Neisseria gonorrhoeae, a Gram-negative
bacterium that elicits more robust genital tract inflammation [19].
Collectively, these clinical, epidemiological, and laboratory find-
ings indicate that C. trachomatis is a weakly antigenic parasite that
elicits mild inflammatory responses and asymptomatically persists
in the female genital tract; thus optimizing its chances for trans-
mission and increasing its survival fitness.
Hypothesis
As T
H
2 differentiation is promoted by weakly antigenic pathogens
and pathogens refractory to eradication by T
H
1andT
H
17 immunity,
we posit that defense against C. trachomatis in the female genital tract
is ultimately regulated by Type 2 immune responses, including T
H
2
immunity, that control chlamydial replication and suppress immu-
nopathological damage to vital reproductive tract structures (Fig. 1).
Testing the hypothesis
To begin exploration of our hypothesis, we completed immuno-
histochemical analyses, with antibodies specific for macrophages,
NK cells, T cells, B cells, and plasma cells, to characterize the leuko-
cyte subpopulations in paraffin-embedded endometrial tissue from
37 uninfected women and 27 women with C. trachomatis genital
tract infection. Among Chlamydia-infected study participants, 17
were diagnosed with endocervical infection alone, and 10 were
diagnosed with both endocervical and endometrial infection [20].
Compared to uninfected women, we found that endocervical C. tra-
chomatis infection was associated with significant increases in
endometrial T cells, B cells, and plasma cells. As the numbers of
endometrial stromal cells positive for CD3 (a pan T cell marker),
but not CD8, were increased among these women, our results also
implied that CD4
+
cells were the T cell subset specifically increased
by endocervical C. trachomatis infection. Ascension of C. trachoma-
tis into the upper genital tract elicited even more substantial in-
crease in the numbers of endometrial CD4
+
T cells, B cells, and
plasma cells compared to when infection was confined to the low-
er genital tract, although infection in these women was also
asymptomatic. While these investigations confirmed that cell
mediated immunity, including increases in CD4
+
T cell numbers,
are elicited by C. trachomatis infection of the female genital tract,
further work is needed to determine the CD4
+
effector cell subsets
specifically selected by evolution to combat Chlamydia infection.
Future studies exploring our hypothesis should define which of
the transcription factors regulating T cell differentiation are prefer-
entially expressed among CD4
+
cells infiltrating the genital tract of
women with C. trachomatis infection. T
H
1 cell differentiation, for
example, is associated with expression of T-bet, a transcription fac-
tor that is considered the master regulator of the T
H
1 response [21].
Similarly, T
H
2 and T
H
17 immunity are driven by host responses that
increase expression of the transcription factors GATA-3 and ROR
c
t,
respectively [22]. We hypothesize that acquisition of C. trachomatis
is associated, at first, with T
H
1 differentiation, and increased T-bet
expression by genital tract CD4
+
T cells. However, as T
H
1 immunity
cannot prevent C. trachomatis from establishing a persistent genital
tract infection, host defense is increasing polarized toward Type 2
responses that dampen tissue inflammation and inhibit collateral
damage to vital reproductive tract anatomy. Thus we also hypoth-
esize that CD4
+
T cells in the genital tract of women with chronic
C. trachomatis infection will preferentially express GATA-3, the
master regulator of T
H
2 immunity. If our hypotheses are correct,
it will then be important to explore if Chlamydia-infected epithelial
cells, or perhaps other innate immune cells, are responsible for
inducing this T
H
2 differentiation.
Accordingly, the effector function of Chlamydia-specific CD4
+
memory T cells isolated from the blood and genital tract of women
with prior or existing genital tract infection should also be examined.
As we predict that initial acquisition of C. trachomatis elicits T
H
1
immunity, a fraction of the CD4
+
memory T cells from these women
are expected to produce IFN-
c
in response to ex vivo stimulation with
chlamydial antigen. However, as we hypothesize that host defense
against C. trachomatis becomes increasingly polarized toward T
H
2
immunity, a significant number of Chlamydia-specific CD4
+
memory
cells are expected to exhibit a T
H
2 phenotype and produce IL-4, IL-5,
and IL-13 in response to similar stimulation. We further predict that
differentiation of Type 2 immunity in women with persistent
C. trachomatis infection will stimulate macrophages to promote
tissue remodeling and repair (as opposed to IFN-
c
activated
macrophages, which show increased microbicidal function) [23–25].
If the studies outlined above determine that host defense in the
genital tract of Chlamydia-infected women becomes polarized to-
ward Type 2 immunity, other work would need to define if these
responses also control C. trachomatis replication in genital tract
epithelial cells. Previous studies showed the IFN-
c
controls growth
of Chlamydia species in vitro by inducing the production of indole-
amine-2,3-dioxygenase, an enzyme that degrades tryptophan, and
hinders Chlamydia spp. growth by tryptophan starvation [26].
However, there is little evidence to support that Chlamydia-specific
T
H
1 immunity is a biologically relevant response in the genital
tract of women, and that chlamydial growth is controlled in vivo
by this mechanism. Among the few studies to examine this ques-
tion, commercial sex workers in Kenya whose peripheral blood
mononuclear cells produced IFN-
c
in response to ex vivo stimula-
tion with chlamydial antigen had increased resistance to C. tracho-
matis genital tract re-infection, but this study was unable to assess
if these protective T
H
1 responses were also associated with in-
creased genital tract inflammation and collateral tissue damage
[27]. However, there is equally little data supporting greater rele-
vance of any other CD4
+
T cell subset. Thus, future studies will also
need to examine the possibility that Type 2 immunity was selected
by evolution to defend against C. trachomatis infection in women as
a means to prevent prolonged or excessive inflammation from
damaging reproductive tract tissue. In conjunction with such stud-
ies, however, is the need to explore the possibility that T
H
2 im-
mune responses can regulate C. trachomatis replication. Although
we hypothesize that T
H
2 immunity will not curb Chlamydia growth
as effectively as T
H
1-mediated tryptophan starvation, such work
has the potential to uncover novel, biologically relevant mecha-
nisms by which T
H
2 immunity inhibits growth of Chlamydia and
other intracellular bacteria. Such possibilities are, of course, now
speculative, but they are consistent with observations that indicate
C. trachomatis genital tract infection of women is asymptomatic,
maintained long-term at low levels of bacterial burden, and only
slowly cleared in the absence of antimicrobial administration.
Hypothesis implications for chlamydial pathogenesis
If correct, our hypothesis would transform C. trachomatis vaccine
development, as much of its current focus is based on the results
2 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
Page 2
from murine models of infection that suggest strong Chlamydia-
specific T
H
1 immunity will be an essential element of an effective
vaccine. However, murine infection rather imprecisely models the
pathogenesis of human C. trachomatis endocervical infection. In
the first place, most of these mice have been intravaginally infected
with C. muridarum, a chlamydia species that is not a natural
pathogen of the murine reproductive tract [28]. Perhaps because
C. muridarum did not evolve as a murine genital tract pathogen,
intravaginal infection stimulates strong innate immune responses
and the differentiation of T
H
1 and T
H
17 immunity [29]. This vigorous
host response typically clears C. muridarum within 1 month of
infection, unlike C. trachomatis, which is more likely to cause chronic
infection in women [30]. In the process of eradicating experimental
intravaginal infection, T
H
1 immunity against C. muridarum also
causes significant damage to the upper genital tract of mice, includ-
ing frequent development of hydrosalpinx (a dilated, fluid-filled
Fallopian tube) [31]. This is in stark contrast to endocervical
infection of women, in which C. trachomatis is only infrequently
responsible for upper genital tract damage [32]. Therefore, use of
the results from murine models to draw conclusions about the
response of women to endocervical C. trachomatis infection has
likely over estimated the biological relevance of T
H
1 immunity.
Although murine infection inadequately models endocervical
C. trachomatis infection of women, it has helped re-enforce the
concepts that animal defense mechanisms co-evolved with a de-
fined set of pathogens and hosts respond to these pathogens in
ways that are optimal for host survival fitness. The T
H
1 response
to C. muridarum rapidly clears infection, but is inappropriate, as
it was not selected by evolution to prevent Fallopian tube dam-
age [33]. The response to C. trachomatis in the genital tract of
women, on the other hand, was selected to prevent uncontrolled
bacterial replication from damaging epithelium as well as
exuberant inflammation from causing immunopathological
destruction of reproductive tract tissue. Because T
H
2 immunity
inhibits the development of more tissue-destructive T
H
1 and
T
H
17 immunity, it may have been the response selected by evo-
lution to combat C. trachomatis and other persistent genital tract
infections. Although the function of Type 2 immunity in defense
against allergens, helminths, and other extracellular pathogens is
established, we now hypothesize that similar type responses also
dampen the intensity of inflammation elicited by chronic
C. trachomatis infection while controlling the growth of this
obligate intracellular bacterium in epithelial tissue of the female
genital tract.
IL-13
IL-13
IL-4
IFN-γ
IL-12
IFN-γ
IL-11
IL-4
IL-4
IL-4
C. trachomatis
elementary bodies
Epithelium
Chlamydial
growth inhibition
Alternative macrophage activation
Wound repair
Inflammatory control
C. trachomatis
reticulate bodies
T
H
1 differentiation
T
H
2 differentiation
T
H
1 cell
Chlamydia-specific antibody production
B cell
T
H
2 cell
Nucleus
Fig. 1. Cartoon depiction of host defense against Chlamydia trachomatis infection in the female genital tract. Although C. trachomatis acquisition induces T
H
1 immune
responses, we hypothesize that persistent infection elicits responses that suppress T
H
1 immunity and polarize host defense toward Type 2 immunity. In response to
persistent infection, we further hypothesize that T
H
2 CD4
+
T cells secrete cytokines which stimulate Chlamydia-specific antibody production, inhibit chlamydial growth, and
activate macrophages that dampen inflammation and promote tissue repair.
R.D. Vicetti Miguel, T.L. Cherpes / Medical Hypotheses xxx (2012) xxx–xxx
3
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
Page 3
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
H
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
H
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
H
1
memory, may warrant greater emphasis. Even more likely,
however, is the possibility that vaccines eliciting appropriate Chla-
mydia-specific, T
H
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
their work.
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
Page 4
  • Source
    • "These data further suggested that the MOMP multiepitope vaccine strongly induces Th cell immune responses to C. trachomatis EB infection, consistent with the previously published studies that Th cell immune response, especially Th1 immune response, is required for protective immunity to clear infection of C. trachomatis and resist to its reinfection in mouse models. However, it has gradually attracted the attention of researchers that Th2 immune response may also play an important role in controlling genital C. trachomatis infection [43]. In this study, the level of IgA antibody in vaginal lavage fluid was distinctly increased in mice immunized with both MOMP multi-epitopes. "
    [Show abstract] [Hide abstract] ABSTRACT: We evaluated the immunogenicity and efficacy of a candidate vaccine comprising the major outer membrane protein (MOMP) multi-epitope of Chlamydia trachomatis. A short gene of multi-epitope derived from MOMP containing multiple T- and B-cell epitopes was artificially synthesized. The recombinant plasmid pET32a(+) containing codon optimized MOMP multi-epitope gene was constructed. Expression of the fusion protein Trx-His-MOMP multi-epitope in Escherichia coli was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot analysis. Balb/c mice were inoculated with the purified fusion protein subcutaneously three times with 2-week intervals. Results showed that the MOMP multi-epitope elicited not only strong humoral immune responses to C. trachomatis by generating significantly high levels of specific antibodies (IgG1 and IgG2a), but also a cellular immune response by inducing robust cytotoxic T lymphocyte responses in mice. Furthermore, the MOMP multi-epitope substantially primed secretion of IFN-γ, revealing that this vaccine could induce a strong Th1 response. Finally, the mice vaccinated with the MOMP multi-epitope displayed a reduction of C. trachomatis shedding upon a chlamydial challenge and an accelerated clearance of the infected C. trachomatis. In conclusion, the MOMP multi-epitope vaccine may have the potentiality for the development of effective prophylactic and therapeutic vaccines against the C. trachomatis infection.
    Preview · Article · Mar 2014 · Acta Biochimica et Biophysica Sinica
    • "However, Th2 polarized cells aid in the production of serum and mucosal IgA antibodies [139, 142, 143, 166, 197], necessary for protection against re-infection [145, 146]. As negative regulators of the Th1 response, Th2 cells may also be involved in regulation [198], minimizing the potential inflammatory damage inherent of Th1 over- expression [199, 200]. Therefore, a vaccine will also need to induce a Th2 response to promote the production of antibodies and to perhaps suppress immunopathology. "
    [Show abstract] [Hide abstract] ABSTRACT: Chlamydia trachomatis is the most common sexually transmitted bacterial infection worldwide. The impact of this pathogen on human reproduction has intensified research efforts to better understand chlamydial infection and pathogenesis. Whilst there are animal models available that mimic the many aspects of human chlamydial infection, the mouse is regarded as the most practical and widely used of the models. Studies in mice have greatly contributed to our understanding of the host-pathogen interaction and provided an excellent medium for evaluating vaccines. Here we explore the advantages and disadvantages of all animal models of chlamydial genital tract infection, with a focus on the murine model and what we have learnt from it so far.
    No preview · Article · Oct 2013 · Current Molecular Medicine
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    [Show abstract] [Hide abstract] ABSTRACT: While Chlamydia trachomatis infections are frequently asymptomatic, mechanisms that regulate host response to this intracellular Gram-negative bacterium remain undefined. This investigation thus used peripheral blood mononuclear cells and endometrial tissue from women with or without Chlamydia genital tract infection to better define this response. Initial genome-wide microarray analysis revealed highly elevated expression of matrix metalloproteinase 10 and other molecules characteristic of Type 2 immunity (e.g., fibrosis and wound repair) in Chlamydia-infected tissue. This result was corroborated in flow cytometry and immunohistochemistry studies that showed extant upper genital tract Chlamydia infection was associated with increased co-expression of CD200 receptor and CD206 (markers of alternative macrophage activation) by endometrial macrophages as well as increased expression of GATA-3 (the transcription factor regulating TH2 differentiation) by endometrial CD4+ T cells. Also among women with genital tract Chlamydia infection, peripheral CD3+ CD4+ and CD3+ CD4- cells that proliferated in response to ex vivo stimulation with inactivated chlamydial antigen secreted significantly more interleukin (IL)-4 than tumor necrosis factor, interferon-c, or IL-17; findings that repeated in T cells isolated from these same women 1 and 4 months after infection had been eradicated. Our results thus newly reveal that genital infection by an obligate intracellular bacterium induces polarization towards Type 2 immunity, including Chlamydia-specific TH2 development. Based on these findings, we now speculate that Type 2 immunity was selected by evolution as the host response to C. trachomatis in the human female genital tract to control infection and minimize immunopathological damage to vital reproductive structures.
    Full-text · Article · Mar 2013 · PLoS ONE
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