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THE ROLE OFTOLL‑LIKE RECEPTOR 9 IN A MURINE MODEL OF CRYPTOCOCCUS GATTII INFECTION
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Resumo em Inglês
Toll-like receptor 9 (TLR9) is crucial to the host immune response against fungi, such as Candida
albicans, Aspergillus fumigatus and Cryptococcus neoformans, but its importance in Cryptococcus
gattii infection is unknown. Our study aimed to understand the role of TLR9 during the course of
experimental C. gattii infection in vivo, considering that the cryptococcal DNA interaction with the
receptor could contribute to host immunity even in an extremely susceptible model. We inoculated
C57BL/6 (WT) and TLR9 knock-out (TLR9−/−) mice intratracheally with 104 C. gattii yeast cells. TLR9−/−
mice had a higher mortality rate compared to WT mice and more yeast cells that had abnormal size,
known as titan cells, in the lungs. TLR9−/− mice also had a greater number of CFUs in the spleen and
brain than WT mice, in addition to having lower levels of IFN-γ and IL-17 in the lung. With these
markers of aggressive cryptococcosis, we can state that TLR9−/− mice are more susceptible to C. gattii,
probably due to a mechanism associated with the decrease of a Th1 and Th17-type immune response
that promotes the formation of titan cells in the lungs. Therefore, our results indicate the participation
of TLR9 in murine resistance to C. gattii infection.
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