# Cryptococcus: History, Epidemiology and Immune Evasion
## 12 Immune Response against Cryptococcosis
### Cell Response against the Infection
In addition to humoral activity, B-1 lymphocytes are capable of acting innately, differentiating themselves in a population of mononuclear phagocytes and fighting the infection caused by _C. neoformans_ in a nitric-oxide-dependent manner; this population is called B-1-Cell-Derived Phagocytes (B-1 CDP) [251] (Figure 3). However, it was demonstrated in the infection of _Paracoccidioides brasiliensis_ that B-1 cells also secrete IL-10 and induce activation of regulatory T cells, facilitating disease progression [252,253]. This contribution of IL-10 production by B-1 cells was also observed in _Leishmania_ and _Francisella_ infections [254, 255, 256]. Therefore, B-1 cells seem to perform their effector function differently in different infections. Furthermore, XID mice have already been described as having increased susceptibility to _C. neoformans_ cryptococcosis [257], and recent data using the same animal model suggest that in the aspect of natural antibody production, the role of IgM produced by B-1 cells seems to be related to the control of infection of _C. neoformans_ and _C. gatti_, preventing its spread from the lungs to the brain and restricting the size of yeasts [187,246]. However, despite having observed the important role that B lymphocytes play in the onset of cryptococcosis, using B lymphocyte depletion and transfer strategies in the infection model caused by _C. neoformans_[244,245], B-1 cell population transfer strategies have not yet been used to demonstrate the effect of its reconstitution and depletion during the experimental model of _C. gatti_ infection. Only a few trials have been conducted with unsatisfactory results using the same strategy in an experimental model of _C. neoformans_ infection [246]. Therefore, B lymphocyte immunity is potentially decisive for the control of cryptococcosis and there are still multiple facets to be explored in this field of study during infection caused by _C. gatti_. Nevertheless, both _C. gatti_ and _C. neoformans_ present distinct features when comparing together their molecular components, epidemiological aspects and immune response; therefore, we summarize some differences between the pathogenic species of _Cryptococcus_ in Table 1. \begin{table}
\begin{tabular}{c c c c} \hline
**Characteristic** & _Cryptococcus neoformans_ & _Cryptococcus guttii_ & **References** \\ \hline Geographic distribution & Found globally in bird feces, trees and soil. & Found in tropical and subtropical areas & [2,5] \\ \hline Infection & Mostly immunocompromised hosts; secondary infection; incubation period around 110 months. & Mostly immunocompetent hosts; primary infection; incubation period from 6 to 7 months. & [3,6,182,183] \\ \hline Serotypes & A, D and AD & B and C. & [17,18] \\ \hline Genotypes & (A) VNI and VNII; (D) VNIV; (AD) VNII; VNB. & (B) VGI and VGI; (C) VGIII and VGIV. & [17,19,20] \\ \hline Cryptococcosis globally & Corresponds around 80\% of infections. & Corresponds \textless{} 20\% of infections. & [3] \\ \hline Culture medium growth & Only uses urea as a nitrogen source, does not grow well in the presence of canvanine. & Can use glycine as a nitrogen source, grows well in the presence of canvanine. & [25,26] \\ \hline Cell wall & H99 strain presents lower chitosan composition; less homogenous melanin distribution. & R265 strain presents higher chitosan composition; more homogenous melanin distribution. & [67] \\ \hline Capsule composition, mannoprotein components, and structural difference & Proportion of (xylose-namnoscope-glucuron acid) by serotypes: (D) 1:3:1 and (A) 2:3:1, & Proportion of (xylose-namnoscope-glucuron acid) by serotypes: (B) 3:3:1 and (C) 4:3:1 & [68,109,120,123,124] \\ \hline _Cryptococcus_ dissemination & More likely to disseminate to the CNS *; less severe disease than _C. gatti_. & More likely to present as pneumonia; a more severe disease. & [171] \\ \hline \end{tabular}
\end{table} 
Table 1: Some differences between _Cryptococcus_ pathogenic species.