Biology Reference
In-Depth Information
Human studies have supplied us with details on proteins that are antigenic and
proteins that are required for the establishment of a strong humoral immune
response. Volunteers challenged with E2348/69 generate antibodies spe-
cific to bundlin, intimin, and O127 LPS (
Donnenberg et al., 1998
;
Fernandes
et al., 2007
). In a separate study, anti-LPS titer was demonstrated to be greatly
decreased when the
eae
gene was deleted (
Donnenberg et al., 1993a
). Diag-
nostic tests on hospitalized infants validated bundlin as immunogenic and also
described the presence of antibodies against EspB (
de Souza Campos Fernandes
et al., 2003
).
An innate immune response to EPEC is initiated by various bacterial prod-
ucts. Flagellin alone has been described as an inducer of IL-8 secretion and
gastroenteritis, mediated by the activation of the NF-κB pathway (
Schüller
et al., 2009
). In addition, LPS, bundlin, EspA, and EspC have been shown to
induce an inflammatory host response (
Edwards et al., 2011
). IL-8 secretion
in response to EPEC infection is concordant with the previously observed
recruitment of neutrophils and macrophages (
Ulshen and Rollo, 1980
). In
mice infected with
C. rodentium
, localization of these cells is due to acti-
vation of the CXCR2 chemokine receptor (
Spehlmann et al., 2009
). In the
Peyer's patch, M cells sample antigens from the intestinal lumen and present
them to specialized antigen-presenting cells within the intraepithelial spaces
of the intestine (
Neutra et al., 1996
) and may transport some pathogens across
the intestinal barrier. Inhibition of EPEC transcytosis by M cells is T3SS-
dependent and is likely due to EspF (
Martinez-Argudo et al., 2007
;
Tahoun
et al., 2011
).
The adaptive response to
C. rodentium
is typically T
H
1-mediated and
involves the production of protective IgG antibodies (
Higgins et al., 1999a,b
;
Bry and Brenner, 2004
). Phagocytosis of
C. rodentium
by macrophages is signif-
icantly impaired by loss of the IgG receptor, Fcγ, highlighting the importance of
this antibody isotype to A/E infection (
Masuda et al., 2008
). However, this mode
of clearance may be inhibited by EPEC, as the effector EspH can inhibit Fcγ
receptor-induced phagocytosis (
Dong et al., 2010
). A balance between a pro-
and anti-immune response is acquired in a T3SS manner, where effector proteins
translocated into the host cell cytoplasm modulate the host response and affect
the activation of inflammatory mediators (see above) (
Sharma et al., 2006
).
Control and prevention
EPEC is transmitted via a fecal-oral route and hence the primary means of pre-
vention include improved sanitation conditions and hygiene. However, there are
other means by which disease onset may be prevented.
Vaccines
Along with EPEC, rotavirus infection represents a major cause of infant diar-
rhea. A rotavirus vaccine is now being introduced into global vaccination
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