Tick saliva affects both proliferation and distribution of Borrelia burgdorferi spirochetes in mouse organs and increases transmission of spirochetes to ticks.

Ixodes ricinus tick saliva-activated transmission of Borrelia burgdorferi sensu stricto spirochetes was studied on the C3H/HeN mouse model. The influence of the feeding of uninfected nymphs on the proliferation and distribution of intradermally inoculated spirochetes was compared with the effect of co-inoculated saliva or salivary gland extract (SGE), respectively. Spirochete loads in murine tissues were evaluated using real-time q-PCR. SGE induced significantly increased spirochete numbers in the skin on the days 4 and 6 post-infection (p.i.). On the other hand, decreased bacterial load in the heart of SGE-treated mice was demonstrated in comparison with control animals. The inoculation of tick saliva increased spirochete load in the urinary bladder on day 6 p.i., while the number of spirochetes in the heart declined on day 6 p.i. The feeding of I. ricinus nymphs raised the spirochete load in the bladder on the days 4 and 6 p.i. On day 6, the number of spirochetes found in the heart was significantly lower than in controls. The prevalence of spirochetes in ticks infected by feeding on mice was more than 10 times higher when the mice were infected with the mixture of spirochetes and saliva or SGE, in comparison with spirochetes alone. The presence of SGE in the infectious inoculum increased the spirochete burden per tick from 0 to almost 28,000. Taken together, these results show a very early effect of tick saliva on the proliferation and distribution of Borrelia spirochetes in the host, probably due to the effect of saliva on the host innate immunity mechanisms.

CD8+ T-cells mediate immunopathology in tick-borne encephalitis.

Epidemics of tick-borne encephalitis involving thousands of humans occur annually in the forested regions of Europe and Asia. Despite the importance of this disease, the underlying basis for the development of encephalitis remains undefined. Here, we prove the key role of CD8(+) T-cells in the immunopathology of tick-borne encephalitis, as demonstrated by prolonged survival of SCID or CD8(-/-) mice, following infection, when compared with immunocompetent mice or mice with adoptively transferred CD8(+) T-cells. The results imply that tick-borne encephalitis is an immunopathological disease and that the inflammatory reaction significantly contributes to the fatal outcome of the infection.

Tick saliva inhibits dendritic cell migration, maturation, and function while promoting development of Th2 responses.

Similarly to other blood-feeding arthropods, ticks have evolved immunosuppressive mechanisms enabling them to overcome the host immune system. Although the immunomodulatory effect of tick saliva on several cell populations of the immune system has been extensively studied, little is known about its impact on dendritic cells (DCs). We have examined the effect of Ixodes ricinus tick saliva on DC function in vitro and in vivo. Exposure of DCs to tick saliva in vitro resulted in impaired maturation, upon CD40 or TLR9, TLR3 and TLR7 ligation, as well as reduced Ag presentation capacity. Administration of tick saliva in vivo significantly inhibited maturation and early migration of DCs from inflamed skin to draining lymph nodes, and decreased the capacity of lymph node DCs to present soluble Ag to specific T cells. Moreover, saliva-exposed DCs failed to induce efficient Th1 and Th17 polarization and promoted development of Th2 responses. Our data reveal a complex inhibitory effect exerted by tick saliva on DC function. Given the role of DCs as the key instigators of adaptive immune responses, alteration of their function might represent a major mechanism of tick-mediated immune evasion.

Higher perceived dominance in Toxoplasma infected men--a new evidence for role of increased level of testosterone in toxoplasmosis-associated changes in human behavior.

Toxoplasma is parasite of cats that uses any warm-blooded animals as intermediate hosts. It is known to induce shifts in behavior, physiology and even morphology of its intermediate hosts, including humans. The lower second to fourth digit ratio (2D:4D ratio) in infected man and women, and higher height in infected man suggest that sex steroid hormones like testosterone could play a role in these shifts. Here, we searched for another indirect indication for a higher postnatal testosterone level, i.e. increased perceived dominance and masculinity in infected men. We showed portrait pictures of 89 male students of which 18 were Toxoplasma-infected to 109 female students. When we statistically corrected for age, men with latent toxoplasmosis were perceived as more dominant (p=0.009) and masculine (p=0.052). These results support the idea that the higher level of testosterone could be responsible for at least some of the toxoplasmosis-associated shifts in human and animal behavior.

Gender differences in behavioural changes induced by latent toxoplasmosis.

There is growing evidence that the protozoan Toxoplasma gondii modifies behaviour of its intermediate hosts, including humans, where it globally infects about 20-60% of the population. Although it is considered asymptomatic in its latent stage, it was previously found to have remarkable and gender different effects on the personality factors A (warmth), G (rule consciousness), L (vigilance, mistrust) and Q3 (self-control, self-image) from Cattell's 16PF Questionnaire. We performed a double blind experiment testing 72 and 142 uninfected men and women, respectively, and 20 and 29 infected men and women, respectively, in order to verify these gender differences using behavioural experiments. Our composite behavioural variables Self-Control and Clothes Tidiness (analogue to the 16PF factors G--conscientiousness and Q3--self-control) showed a significant effect of the toxoplasmosis-gender interaction with infected men scoring significantly lower than uninfected men and a trend in the opposite direction in women. The effect of the toxoplasmosis-gender interaction on our composite behavioural variable Relationships (analogue to factor A--warmth) approached significance; infected men scored significantly lower than uninfected men whereas there was no difference in women. In the composite behavioural variable Mistrust (analogue to factor L), the pattern was affected by environment (rural versus urban). Possible interpretations of the gender differences are discussed.

Decreased level of novelty seeking in blood donors infected with Toxoplasma.

OBJECTIVES: Toxoplasma gondii, a parasitic protozoan, infects about 30 - 60% of people worldwide. Toxoplasma is known to induce behavioral changes and an increase of dopamine in mice. The presence of anti-Toxoplasma antibodies (latent toxoplasmosis) is also a risk factor for schizophrenia. Latent toxoplasmosis in men (male soldiers) is associated with lower novelty seeking. As the novelty seeking is supposed to negatively correlate with level of dopamine, the observed effect was interpreted as indirect evidence of increased dopamine levels in subjects with toxoplasmosis. However, it is also possible that the observed effect was caused by association of both novelty seeking and Toxoplasma infection with a third factor, e.g. size of place of residence. METHODS: Personality profile of 290 blood donors (205 men and 85 women) were measured by Cloninger's TCI (Temperament and Character Inventory) and their blood samples were assayed for the presence of anti-Toxoplasma antibodies. Difference between Toxoplasma-infected and Toxoplasma-free subjects was tested with ANCOVA method with gender, size of place of residence, and age as covariates. RESULTS: The present analysis revealed that lower novelty seeking was associated with latent toxoplasmosis both in men and women. The effect of infection on novelty seeking remained significant even after adjustment for size of place of residence (p<0.01). CONCLUSION: Decreased novelty seeking in Toxoplasma-infected subjects have been already confirmed in three independent populations (male soldiers and male and female blood donors). These findings suggest that the local inflammation-induced increase in dopamine in the brain of infected subjects can represent a missing link between toxoplasmosis and schizophrenia.