Is Cryptococcus gattii a Primary Pathogen?

Abstract

The two etiologic agents of cryptococcal meningoencephalitis, Cryptococcus neoformans and C. gattii, have been commonly designated as either an opportunistic pathogen for the first species or as a primary pathogen for the second species. Such a distinction has been based on epidemiological findings that the majority of patients presenting meningoencephalitis caused by C. neoformans are immunocompromised while C. gattii infection has been reported more often in immunocompetent patients. A recent report, however, showed that GM-CSF (granulocyte-macrophage colony-stimulating factor) neutralizing antibodies were prevalent in the plasma of “apparently immunocompetent” C. gattii patients with meningoencephalitis. Because GM-CSF is essential for differentiation of monocytes to macrophages and modulating the immune response, it is not surprising that the lack of GM-CSF function predisposes otherwise healthy individuals to infection via inhalation of environmental pathogens such as C. gattii. Since the test for anti-GM-CSF autoantibodies is not included in routine immunological profiling at most hospitals, healthy patients with GM-CSF neutralizing antibodies are usually categorized as immunocompetent. It is likely that a comprehensive immunological evaluation of patients with C. gattii meningoencephalitis, who had been diagnosed as immunocompetent, would reveal a majority of them had hidden immune dysfunction. This paper reviews the relationship between GM-CSF neutralizing antibodies and the risk for C. gattii infection with CNS involvement.

The significance of anti‐granulocyte‐macrophage colony‐stimulating factor antibodies in cryptococcal infection: case series and review of antibody testing

“…Saijo et al . demonstrated that GM‐CSF antibodies are predominantly associated with infection with the C. gatti species, as reinforced by our cases, although the reason for this specific sub‐species association remains unclear . In 2013, Rosen et al .…”

“…7 Saijo et al demonstrated that GM-CSF antibodies are predominantly associated with infection with the C. gatti species, as reinforced by our cases, although the reason for this specific sub-species association remains unclear. 11,12 In 2013, Rosen et al 13 screened for GM-CSF antibodies in four current and 103 archived plasma/CSF samples from HIV-negative cryptococcal meningitis patients. Neutralising GM-CSF antibodies were detected in the four current patients and an additional three archived samples, but not in healthy or disease controls.…”

An Association of Cryptococcus Neoformans/C. gattii Genotype and HIV Status in Asia: A Systematic Review

“…1 It is known that C. neoformans is associated mainly with immunosuppression, especially among HIV-infected patients, while C. gattii generally causes cryptococcosis in immunocompetent patients. 2 However, some reports have demonstrated contradictory results. Recent studies from China and South Korea showed that most of cryptococcosis patients caused by C. neoformans were HIV-negative patients without other immunocompromised conditions.…”

First Autochthonous Case of Cryptococcal Meningitis in an Immunocompetent Host Due to Cryptococcus gattii VGIin Northern Italy

“…Although in our case, the patient was considered immunocompetent on the basis of classical immunological tests (immunoglobulin dosage and lymphocyte subpopulation analysis); other immune diseases, not detected by the above methods, cannot be excluded. For example, some authors report that the presence of antibodies antigranulocyte-macrophage colony-stimulating factor (GM-CSF), not investigated in our case, could be a predisposing condition for C. gattii infection [20]. Detection of anti-GM-CSF antibodies should be encouraged in cryptococcosis cases due to C. gattii strains in order to elucidate the relationship This study between the expression of this factor and the progress of the fungal disease.…”