Abstract
Immune responses to
Chlamydia trachomatis
underlay both immunity and immunopathology. Immunopathology in turn has been attributed to chronic persistent infection with persistence being defined as the presence of organisms in the absence of replication. We hypothesized that dendritic cells (DCs) play a central role in
Chlamydia
immunity and immunopathology by favoring the long-term survival of
C. muridarum
. This hypothesis was examined based on (i) direct staining of
Chlamydia
in infected DCs to evaluate the development of inclusions, (ii) titration of infected DCs on HeLa cells to determine cultivability, and (iii) transfer of
Chlamydia
-infected DCs to naive mice to evaluate infectivity. The results show that
Chlamydia
survived within DCs and developed both typical and atypical inclusions that persisted in a subpopulation of DCs for more than 9 days after infection. Since the cultivability of
Chlamydia
from DCs onto HeLa was lower than that estimated by the number of inclusions in DCs, this suggests that the organisms may be in state of persistence. Intranasal transfer of long-term infected DCs or DCs purified from the lungs of infected mice caused mouse lung infection, suggesting that in addition to persistent forms, infective
Chlamydia
organisms also developed within chronically infected DCs. Interestingly, after in vitro infection with
Chlamydia
, most DCs died. However,
Chlamydia
appeared to survive in a subpopulation of DCs that resisted infection-induced cell death. Surviving DCs efficiently presented
Chlamydia
antigens to
Chlamydia
-specific CD4
+
T cells, suggesting that the bacteria are able to both direct their own survival and still allow DC antigen-presenting function. Together, these results raise the possibility that
Chlamydia
-infected DCs may be central to the maintenance of T-cell memory that underlies both immunity and immunopathology.