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2015 ; 83
(4
): 1523-35
Nephropedia Template TP
gab.com Text
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English Wikipedia
Rab14 regulates maturation of macrophage phagosomes containing the fungal
pathogen Candida albicans and outcome of the host-pathogen interaction
#MMPMID25644001
Okai B
; Lyall N
; Gow NA
; Bain JM
; Erwig LP
Infect Immun
2015[Apr]; 83
(4
): 1523-35
PMID25644001
show ga
Avoidance of innate immune defense is an important mechanism contributing to the
pathogenicity of microorganisms. The fungal pathogen Candida albicans undergoes
morphogenetic switching from the yeast to the filamentous hyphal form following
phagocytosis by macrophages, facilitating its escape from the phagosome, which
can result in host cell lysis. We show that the intracellular host trafficking
GTPase Rab14 plays an important role in protecting macrophages from lysis
mediated by C. albicans hyphae. Live-cell imaging of macrophages expressing green
fluorescent protein (GFP)-tagged Rab14 or dominant negative Rab14, or with small
interfering RNA (siRNA)-mediated knockdown of Rab14, revealed the temporal
dynamics of this protein and its influence on the maturation of macrophage
phagosomes following the engulfment of C. albicans cells. Phagosomes containing
live C. albicans cells became transiently Rab14 positive within 2 min following
engulfment. The duration of Rab14 retention on phagosomes was prolonged for
hyphal cargo and was directly proportional to hyphal length. Interference with
endogenous Rab14 did not affect the migration of macrophages toward C. albicans
cells, the rate of engulfment, the overall uptake of fungal cells, or early
phagosome processing. However, Rab14 depletion delayed the acquisition of the
late phagosome maturation markers LAMP1 and lysosomal cathepsin, indicating
delayed formation of a fully bioactive lysosome. This was associated with a
significant increase in the level of macrophage killing by C. albicans.
Therefore, Rab14 activity promotes phagosome maturation during C. albicans
infection but is dysregulated on the phagosome in the presence of the invasive
hyphal form, which favors fungal survival and escape.