Identification of App1 as a regulator of phagocytosis and virulence of Cryptococcus neoformans
J. Clin. Invest. Chiara Luberto, et al. 112:1080 doi:10.1172/JCI18309 [
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Figure 4App1 regulates phagocytosis of
C. neoformans. (
a and
b) Absence of App1 (
Δapp1) increases attached and ingested cells by AMs. Reconstitution of
APP1 gene (
Δapp1Rec) as well as treatment with App1 recombinant protein restores the WT phenotype (
a) as compared with the control (
b). (
c) App1 treatment decreases phagocytosis of
C. neoformans WT cells. (
d) Ex vivo phagocytosis. Downregulation of Ipc1 and absence of App1 increase phagocytosis of fungal cells by AMs after 2 hours of infection as compared with the WT strain.
IPC1Rec and
Δapp1Rec strains reconstitute the WT phenotype. (
e) App1 does not inhibit phagocytosis of antibody-coated erythrocytes. (
f) Treatment with App1 inhibits phagocytosis of iC3b/IgM-IgG–coated erythrocytes. WT, WT
C. neoformans H99 strain;
Δapp1,
C. neoformans lacking App1 protein;
Δapp1Rec,
Δapp1 reconstituted strain;
IPC1Rec, Ipc1 reconstituted strain; App1 1×, 8 ng of App1 recombinant protein plus 14 ng of contaminating proteins; App1 2×, 3×, 4×, and 5×, two-, three-, four-, and fivefold App1 1× concentration; control 1×, 14 ng of contaminating proteins; control 2×, 3×, 4×, and 5×, two-, three-, four-, and fivefold control 1× concentration.