AIM2 enhances Candida albicans infection through promoting macrophage apoptosis via AKT signaling
Candida albicans is among the most prevalent invasive fungal pathogens for immunocompromised individuals and novel therapeutic approaches that involve immune response modulation are imperative. Absent in melanoma 2 (AIM2), a pattern recognition receptor for DNA sensing, is well recognized for its in...
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Published in | Cellular and molecular life sciences : CMLS Vol. 81; no. 1; p. 280 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Cham
Springer International Publishing
01.12.2024
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | Candida albicans
is among the most prevalent invasive fungal pathogens for immunocompromised individuals and novel therapeutic approaches that involve immune response modulation are imperative. Absent in melanoma 2 (AIM2), a pattern recognition receptor for DNA sensing, is well recognized for its involvement in inflammasome formation and its crucial role in safeguarding the host against various pathogenic infections. However, the role of AIM2 in host defense against
C. albicans
infection remains uncertain. This study reveals that the gene expression of AIM2 is induced in human and mouse innate immune cells or tissues after
C. albicans
infection. Furthermore, compared to their wild-type (WT) counterparts,
Aim2
−/−
mice surprisingly exhibit resistance to
C. albicans
infection, along with reduced inflammation in the kidneys post-infection. The resistance of
Aim2
−/−
mice to
C. albicans
infection is not reliant on inflammasome or type I interferon production. Instead,
Aim2
−/−
mice display lower levels of apoptosis in kidney tissues following infection than WT mice. The deficiency of AIM2 in macrophages, but not in dendritic cells, results in a phenocopy of the resistance observed in
Aim2
−/−
mice against
C. albican
infection. The treatment of Clodronate Liposome, a reagent that depletes macrophages, also shows the critical role of macrophages in host defense against
C. albican
infection in
Aim2
−/−
mice. Furthermore, the reduction in apoptosis is observed in
Aim2
−/−
mouse macrophages following infection or treatment of DNA from
C. albicans
in comparison with controls. Additionally, higher levels of AKT activation are observed in
Aim2
−/−
mice, and treatment with an AKT inhibitor reverses the host resistance to
C. albicans
infection. The findings collectively demonstrate that AIM2 exerts a negative regulatory effect on AKT activation and enhances macrophage apoptosis, ultimately compromising host defense against
C. albicans
infection. This suggests that AIM2 and AKT may represent promising therapeutic targets for the management of fungal infections. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1420-682X 1420-9071 1420-9071 |
DOI: | 10.1007/s00018-024-05326-9 |