HBEC30 or A549 cells were plated on 96 well plates overnight. Media was removed and replaced with media containing SB218078 (1mM, 100nM 10nM) 3-IPEHPC (12.5mM, 1.25mM, 125nM) DMSO (0.06%) or plain media. Cells were incubated overnight and then infected with WSN at an MOI of 5. Cells were fixed with 4% formaldehyde at 8 hours, 12 hours and 24 hours post infection and stained as described previously. SB218078 was purchased from Tocris biosciences cat # 2560 and dissolved in DMSO. 3-IPEHPC was dissolved in PBS. Figure S1 Individual siRNA oligo assays. HBEC30 cells were transfected in triplicate with four individual siRNA oligos and infected with WSN. Cell viability was measured 48 hours post infection and a two-tailed Student's t-test was performed to determine significance. Green boxes are oligos with a p value less than 0.05. (PDF) Figure S2 Network analysis of siRNA screen results. Data from siRNA screen results was used for NetWalk analysis. Nodes are colored based on Z-Score with red for positive and green for negative, edges are colored based on interactions, PPI: protein-protein interaction, TF-Target: gene regulation, GO: GO similarity. Networks analysis was performed with entire data set. (PDF)  Association of Fcγ Receptor IIB Polymorphism with Cryptococcal Meningitis in HIV-Uninfected Chinese Patients BACKGROUND: As important regulators of the immune system, the human Fcγ receptors (FcγRs) have been demonstrated to play important roles in the pathogenesis of various infectious diseases. The aim of the present study was to identify the association between FCGR polymorphisms and cryptococcal meningitis. METHODOLOGY/PRINCIPAL FINDINGS: In this case control genetic association study, we genotyped four functional polymorphisms in low-affinity FcγRs, including FCGR2A 131H/R, FCGR3A 158F/V, FCGR3B NA1/NA2, and FCGR2B 232I/T, in 117 patients with cryptococcal meningitis and 190 healthy controls by multiplex SNaPshot technology. Among the 117 patients with cryptococcal meningitis, 59 had predisposing factors. In patients with cryptococcal meningitis, the FCGR2B 232I/I genotype was over-presented (OR = 1.652, 95% CI [1.02–2.67]; P = 0.039) and the FCGR2B 232I/T genotype was under-presented (OR = 0.542, 95% CI [0.33–0.90]; P = 0.016) in comparison with control group. In cryptococcal meningitis patients without predisposing factors, FCGR2B 232I/I genotype was also more frequently detected (OR = 1.958, 95% CI [1.05–3.66]; P = 0.033), and the FCGR2B 232I/T genotype was also less frequently detected (OR = 0.467, 95% CI [0.24–0.91]; P = 0.023) than in controls. No significant difference was found among FCGR2A 131H/R, FCGR3A 158F/V, and FCGR3B NA1/NA2 genotype frequencies between patients and controls. CONCLUSION/SIGNIFICANCE: We found for the first time associations between cryptococcal meningitis and FCGR2B 232I/T genotypes, which suggested that FcγRIIB might play an important role in the central nervous system infection by Cryptococcus in HIV-uninfected individuals. Cryptococcal meningitis is the most common opportunistic fungal infection of the central nervous system in AIDS patients. Among HIV-uninfected patients, several predisposing factors for cryptococcal meningitis such as corticosteroid medication, solid organ transplantation and malignancy, etc, have been indentified. Yet cryptococcal infections in apparently healthy individuals are also increasingly being reported, especially from Asian data [1] [2] [3] . Our previous study has demonstrated an association between mannose-binding lectin (MBL) genetic deficiency and cryptococcal meningitis in HIV-uninfected patients [4] . However, MBL deficiency was present in only 21% of the cases, and for the remaining 79% of patients the underlying mechanism for susceptibility remained unclear.