Human immune polymorphisms associated with the risk of cryptococcal disease

Abstract

Cryptococcus neoformans is an opportunistic fungal pathogen that can cause lethal cryptococcal meningitis in immunocompromised individuals such as those with HIV/AIDS. In addition, cryptococcal infections occasionally arise in immunocompetent individuals or those with previously undiagnosed immunodeficiencies. The course of cryptococcosis is highly variable in both patient groups, and there is rapidly growing evidence that genetic polymorphisms may have a significant impact on the trajectory of disease. Here, we review what is currently known about the nature of these polymorphisms and their impact on host response to C. neoformans infection.Thus far, polymorphisms in Fc gamma receptors, mannose-binding lectin, Dectin-2, Toll-like receptors and macrophage colony-stimulating factor have been associated with susceptibility to cryptococcal disease. Notably, however, in some cases the impact of these polymorphisms depends on the genetic background of the population; for example, the FCGR3A 158 F/V polymorphism was associated with an increased risk of cryptococcal disease in both HIV-positive and HIV-negative white populations, but not in Han Chinese patients. In most cases, the precise mechanism by which the identified polymorphisms influence disease progression remains unclear, although impaired fungal recognition and phagocytosis by innate immune cells appears to play a major role. Finally, we highlight outstanding questions in the field and emphasize the need for future research to include more diverse populations in their genetic association studies.

Differential and cooperative effects of IL-25 and IL-33 on T helper cells contribute to cryptococcal virulence and brain infection

“…Related studies indicated that C. neoformans clinical isolates that were more easily phagocytosed by macrophages (termed high-uptake C. neoformans ) were associated with higher fungal burden in the brain 24 , 25 . Our previous study also suggested that C. neoformans with a high-uptake rate (HU) exhibited an increasing ability to disseminate to the brain than those with a low-uptake rate (LU), and this ability was associated with elevated type-2 cytokine production 26 .…”

Isolated Cryptococcal Infection of the Thoracic Spine in an Immunocompetent Patient

“…Studies have shown that cryptococcal infection of the bone is more common in patients with immune insufficiency, 2 , 3 including HIV infection 4 or serious immunodeficiency with long-term use of immunosuppressants, as well as diabetes, 5 sarcoidosis, 6 tuberculosis, 7 lymphopenia, 8 rheumatoid arthritis 9 and other related immunodeficiencies. In 1955, Eisen et al 10 reported a case of cryptococcosis with lung and spinal involvement.…”

Role of TLRs in HIV-1 Infection and Potential of TLR Agonists in HIV-1 Vaccine Development and Treatment Strategies

“…Likewise, comparing TLR2 alleles (2180 C/T) across various patient groups failed to find statistically significant changes in their frequency [ 59 ]. TLR1 rs5743563 T/T, TLR2 rs3804099 T/T, TLR6 rs3796508 G/A, and TLR6 rs3804099 C/T were associated with a higher risk of cryptococcal meningitis in HIV-negative patients, whereas rs5743563 and rs3804099 were associated with CSF cytokine expression [ 60 ].…”