Intranasal inoculation of Cryptococcus neoformans in mice produces nasal infection with rapid brain dissemination

Cryptococcus neoformans is an important fungal pathogen, causing lifethreatening pneumonia and meningoencephalitis. Brain dissemination of C. neoformans is thought to be a consequence of an active infection in the lung which then extravasates to other sites. Brain invasion results from dissemination via either transport by free yeast cells in the bloodstream or Trojan horse transport within mononuclear phagocytes. We assessed brain dissemination in three mouse models of infection: intravenous, intratracheal, and intranasal models. All three modes of infection resulted in dissemination of C. neoformans to the brain in less than 3 h. Further, C. neoformans was detected in the entirety of the upper respiratory tract and the ear canals of mice. In recent years, intranasal infection has become a popular mechanism to induce pulmonary infection because it avoids surgery, but our findings show that instillation of C. neoformans produces cryptococcal nasal infection. These findings imply that immunological studies using intranasal infection should assume that the initial sites of infection of infection are brain, lung, and upper respiratory tract, including the nasal airways.