Chlamydial infections in animals
Chlamydophila abortus : Immune
responses
Many early investigations on immune responses and vaccine studies focused on the use of inactivated strains of
chlamydiae and protection against challenge in animal models. Local and systemic antibody responses have been produced by genital infection in the mouse, guinea pig and monkey
(Rank et al., 1985; Patton et al.,
1983), eye infection in the guinea pig (Murray et al.,
1973) and lung infection in the mouse (Williams et al.,
1984). The best defined model of immunity to chlamydiae is represented by murine genital tract infection with the mouse pneumonitis
(MoPn) strain, i.e. Chlamydia muridarum. The latter is a model of progressive chlamydial infection involving
lower and upper genital tract that
partially mimics chlamydial genital tract infections in women [see vaccine
development].
In ruminants, C. abortus infections can result in single episode diseases such as abortion, whereas C. pecorum infections cause chronic diseases such as arthritis and conjunctivitis. In a study of the humoral immune response to C. abortus abortion infection in sheep,
Krauss et al. (1986) showed that IgG1 was dominant.
In cattle the dominant subclass was IgG2 (Schmeer et al.,
1987). A range of immunoreactive antigens in C. abortus strains were identified in immunoblotting studies with sera from aborted ewes
(Huang et al., 1990; Griffiths et al.,
1992). These included the major outer membrane protein
(MOMP) and a group of higher molecular weight proteins, probably corresponding
to the polymorphic outer membrane proteins (POMPs).In both abortion and the chronic-type diseases, there is persistent or latent infection, which can become activated by trauma, pregnancy or other factors. Mice infected with C. abortus demonstrated
an increased expression of MHC class II antigens on macrophages (Paulnock et al.,
1986), which may play a role in generating
cell mediated immune responses to the infection. C. psittaci infection
of macrophages has immunomodulatory effects (Lammert,
1982) affecting such normal functions as antigen presentation.
Cell mediated immunity to C. abortus abortion infection in sheep has been demonstrated by
delayed type hypersensitivity (DTH) reactions to skin tests (Wilsmore et al.,
1984; Dawson et al., 1986). Ewes that aborted developed positive DTH
reactions. However, C. abortus infection did not generate DTH responses in some non-pregnant ewes. Sheep with poor DTH responses following vaccination were more likely to abort after challenge with C. abortus,
suggesting that cell mediated immunity as measured by DTH responses might be
protective. No correlation was found between immunity and the presence of genus
specific, anti-lipopolysaccharide (LPS) antibodies detected by the complement fixation test
(CFT). The limited data suggest that the generation of a CMI response may be important in resistance
to chlamydial infection and subsequent colonisation of the placenta.
Persistent, subclinical C. abortus infection in non-pregnant sheep is a feature of ovine chlamydial
abortion. Detection of the presence of the organism is difficult. Low-level production of the cytokine interferon-g
(IFN-g
) resulting from "antigen pulsing" could assist in the maintenance of a persistent state
of chlamydial infection (Brown and
Entrican, 1996). Immunity following abortion in sheep is likely to result from the massive antigenic stimulation due to C. abortus replication in the placenta. During pregnancy in sheep the immune system becomes biased towards a type 2 helper T cell (Th2) subset response, in which IL-4 and
IL-10 antagonise and down-regulate Th1 cytokines, notably IFN-g
. This down-regulation might allow chlamydiae, previously held in a persistent state by
IFN-g
chlamydiastasis, to colonise the placenta causing foetal damage and abortion
[see interferon and persistent infection].
Future research efforts are likely to concentrate on protective Th1-like
cell mediated immune responses, generated during infection with whole organisms.
Efforts will also be necessary to establish the most appropriate vaccine
antigens [see: vaccine development]. In addition, the roles for various cytokines in resolving disease and for cytotoxic T cells in the exacerbation of
or recovery from disease need to be defined (Rasmussen,
1998).
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