Genetic Susceptibility to Chlamydia trachomatis Determines the Outcome of the Disease Data from a Mouse Model

Immunoblotting obtained with sera of BALB/c and C3H mice collected after immunizations with C. trachomatis are displayed in Figure 13.4. Blots with pre-im-mune sera were blank (data not shown); on the other hand, blots with immune sera collected at 15, 23, 37, and 53 days post-infection exhibited reproducible patterns of immunoreactive spots. It has also become evident that in the two groups of mice, which have developed different diseases, humoral immune response was different. In BALB/c mice, which had a transient salpingitis without infertility, the immune response started very fast, especially against the MOMP. On the other hand in C3H mice, which become chronically ill and infertile, the response was quite slow, with, at the end, a different pattern of immunostained antigens, such as OMP2, GroEL-like protein and EF-Tu.

These results suggest that a different immune response can be correlated with different outcome of the disease. In particular we have focused attention on the time course of two of the well-studied antigens, such as MOMP and OMP2. As reported in Figure 13.5 a the histogram associated with the immunoreactivity time course of MOMP in the two different strains of mice showed different immune responses. Indeed in BALB/c the immunostaining of MOMP revealed a rapid increase in expression reaching a high intensity, whereas in C3H the increase was slower and reached an intensity of immunostaining lower than in BALB/c. Instead, OMP2 was immunostained only in the C3H mice as shown in the histogram of Figure 13.5 b. From these last results it is clear that different antibodies may be associated with protective or pathological immune responses. For example, a very fast and high response to MOMP is associated with healing, as BALB/c mice do not develop chronic salpingitis. On the other hand, antibodies against OMP2, GroEL-like protein, and EF-Tu play an important role in directing the disease in a chronic state. This observation has been already reported for GroEL-like protein which was associated with chlamydial disease pathogenesis [41, 42]. In the two strains of mice, genetically different as to susceptibility to the disease [43], we also found different antibody responses to pathogen proteins.

Animal models allow comparison of experimental data with data on human immune responses due to natural infections. Actually, in our study, the antibody immune responses in mice are very similar to those observed in patients. As reported in Figure 13.6, C3H mice, which become chronically sick, show a similar immune response to that in humans with chronic salpingitis. Both human and C3H sera immunoreacted with OMP2, GroEL-like protein, and EF-Tu. On the other hand, BALB/c mice, which develop a mild form of disease, raised a different immune response, comprising antibodies specific for different chlamydial proteins.

In conclusion the host immune response to infectious agents may be of primary importance. The description of the immunoproteome, most frequently exploited in vaccine discovery, also correlates the hosts antibody responses, either protective or pathogenic, with the outcome of the disease. This kind of research is aimed at the development of new diagnostic/prognostic markers.

BALB/c C3H

Figure 13.4 Immunoblots with mouse sera collected at 15, 23, 37 and 53 days post-immunization in the two different strains of mice analyzed (BALB/c and C3H).

BALB/c C3H

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