Intranasal Inoculation of Cryptococcus neoformans in Mice Produces Nasal Infection with Rapid Brain Dissemination.

is an important fungal pathogen, causing life-threatening pneumonia and meningoencephalitis. Brain dissemination of 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 to the brain in less than 3 h. Further, 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 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. causes an estimated 181, 000 deaths each year, mostly associated with untreated HIV/AIDS. has a ubiquitous worldwide distribution. Humans become infected from exposure to environmental sources, after which the fungus lays dormant within the human body. Upon AIDS-induced immunosuppression or therapy-induced immunosuppression (required for organ transplant recipients or those suffering from autoimmune disorders), cryptococcal disease reactivates and causes life-threatening meningitis and pneumonia. This study showed that upon contact with the host, can quickly (a few hours) reach the host brain and also colonizes the nose of infected animals. Therefore, this work paves the way to better knowledge of how travels through the host body. Understanding how infects, disseminates, and survives within the host is critically required so that we can prevent infections and the disease caused by this deadly fungus.