PMID- 15385488
OWN - NLM
STAT- MEDLINE
DCOM- 20041025
LR  - 20240510
IS  - 0019-9567 (Print)
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Linking)
VI  - 72
IP  - 10
DP  - 2004 Oct
TI  - Dysregulated inflammatory response to Candida albicans in a C5-deficient mouse 
      strain.
PG  - 5868-76
AB  - Experimental infection of inbred mouse strains with Candida albicans provides a 
      good model system to identify host genetic determinants that regulate onset of, 
      response to, and ultimate outcome of disseminated candidiasis. The A/J mouse 
      strain is exquisitely sensitive to infection with C. albicans, while the C57BL/6J 
      strain is relatively resistant, as measured by survival following intravenous 
      injection of Candida blastospores. This differential susceptibility is caused by 
      an A/J-specific loss-of-function mutation in the C5 component of the complement 
      pathway. C5 plays several critical roles in host response to infection, including 
      target lysis and phagocyte recruitment. Therefore, to determine which of its 
      functions were required for host resistance to candidiasis, a detailed 
      comparative analysis of pathophysiology and host response to acute C. albicans 
      infection was conducted in A/J and C57BL/6J mice. C5-sufficient C57BL/6J mice 
      were found to succumb late in infection due to severe kidney pathology, typified 
      by fungal replication and robust neutrophil-based inflammatory response 
      associated with extensive tissue damage. In contrast, A/J mice were moribund 
      within 24 h postinfection but displayed little if any kidney damage despite an 
      inability to mobilize granulocytes and a high fungal load in the kidney. Rather, 
      C5 deficiency in A/J mice was associated with higher levels of circulating 
      cytokines tumor necrosis factor alpha, interleukin-6, monocyte chemotactic 
      protein 1 (MCP-1), MCP-5, and eotaxin in response to C. albicans. Transfer of the 
      C5-defective allele from A/J onto a C57BL/6J genetic background in recombinant 
      congenic strain BcA17 recapitulated the phenotypic aspects of the susceptibility 
      of A/J mice to C. albicans, confirming the causative role of C5 deficiency in the 
      dysregulated cytokine response.
FAU - Mullick, Alaka
AU  - Mullick A
AD  - Biotechnology Research Institute, National Research Council, Montreal, Quebec, 
      Canada. alaka.mullick@cnrc-nrc.gc.ca
FAU - Elias, Miria
AU  - Elias M
FAU - Picard, Serge
AU  - Picard S
FAU - Bourget, Lucie
AU  - Bourget L
FAU - Jovcevski, Orce
AU  - Jovcevski O
FAU - Gauthier, Susan
AU  - Gauthier S
FAU - Tuite, Ashleigh
AU  - Tuite A
FAU - Harakidas, Penelope
AU  - Harakidas P
FAU - Bihun, Craig
AU  - Bihun C
FAU - Massie, Bernard
AU  - Massie B
FAU - Gros, Philippe
AU  - Gros P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Complement C5)
RN  - 0 (Cytokines)
SB  - IM
MH  - Animals
MH  - Animals, Congenic
MH  - Candida albicans/*immunology
MH  - Candidiasis/blood/*immunology/*pathology/physiopathology
MH  - Complement C5/*deficiency/genetics/immunology
MH  - Cytokines/blood/immunology
MH  - Inflammation/blood/*immunology/pathology/physiopathology
MH  - Kidney/physiopathology
MH  - Mice
MH  - Mice, Inbred A
MH  - Mice, Inbred C57BL
MH  - Species Specificity
PMC - PMC517586
EDAT- 2004/09/24 05:00
MHDA- 2004/10/27 09:00
PMCR- 2004/10/01
CRDT- 2004/09/24 05:00
PHST- 2004/09/24 05:00 [pubmed]
PHST- 2004/10/27 09:00 [medline]
PHST- 2004/09/24 05:00 [entrez]
PHST- 2004/10/01 00:00 [pmc-release]
AID - 72/10/5868 [pii]
AID - 0810-04 [pii]
AID - 10.1128/IAI.72.10.5868-5876.2004 [doi]
PST - ppublish
SO  - Infect Immun. 2004 Oct;72(10):5868-76. doi: 10.1128/IAI.72.10.5868-5876.2004.