PMID- 32692841
OWN - NLM
STAT- MEDLINE
DCOM- 20210101
LR  - 20210101
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 61
IP  - 8
DP  - 2020 Jul 1
TI  - Indoleamine 2,3-Dioxygenase Regulates Macrophage Recruitment, Polarization and 
      Phagocytosis in Aspergillus Fumigatus Keratitis.
PG  - 28
LID - 10.1167/iovs.61.8.28 [doi]
LID - 28
AB  - PURPOSE: To explore the influence of indoleamine 2,3-dioxygenase (IDO) on 
      macrophage recruitment, polarization and phagocytosis in Aspergillus fumigatus 
      keratitis. METHODS: A murine model of A. fumigatus keratitis and peritoneal 
      macrophages incubated with the hyphae of A. fumigatus were used. Macrophage 
      recruitment in corneas was evaluated using immunofluorescence staining. The 
      polarization of macrophages, which was stimulated by A. fumigatus and 
      pretreatment with or without 1-methyltryptophan (1-MT), interferon gamma (IFNG), 
      extracellular regulated protein kinases (ERK) antagonist, and p38 antagonist, was 
      determined using reverse-transcription polymerase chain reaction and flow 
      cytometry. P38 and ERK levels were determined using Western blotting. Macrophage 
      phagocytosis was examined using colony-forming units. RESULTS: Compared with the 
      A.F. group, recruitment of macrophages increased, tumor necrosis factor-alpha (TNF-alpha) 
      and inducible nitric oxide synthase (iNOS) expression decreased, whereas 
      arginase-1 (Arg-1) and interleukin-10 (IL-10) expression increased in the mouse 
      corneas of the 1-MT+A.F. group. The ratio of CD206+/CD86+ macrophages in the 
      corneas and spleens of 1-MT+A.F. group increased. Furthermore, in peritoneal 
      macrophages stimulated by A. fumigatus, 1-MT promoted Arg-1 and IL-10 expression 
      while upregulating the ratio of CD206+/CD86+ macrophages. Conversely, IDO agonist 
      IFNG promoted TNF-alpha and iNOS expression, inhibited Arg-1 and IL-10 expression and 
      downregulated the ratio of CD206+/CD86+ macrophages. The role of IFNG was 
      reversed by the antagonist of P38 or ERK. P38 and ERK levels were downregulated 
      in corneas of 1-MT+A.F. group. Besides, IFNG inhibited macrophage phagocytosis. 
      CONCLUSION: IDO inhibited macrophage recruitment and phagocytosis in A. fumigatus 
      keratitis. Mechanistically, IDO is involved in M1 macrophage polarization in A. 
      fumigatus keratitis through a MAPK/ERK-dependent pathway.
FAU - Jiang, Nan
AU  - Jiang N
AD  - ,.
FAU - Zhang, Li
AU  - Zhang L
AD  - ,.
FAU - Zhao, Guiqiu
AU  - Zhao G
AD  - ,.
FAU - Lin, Jing
AU  - Lin J
AD  - ,.
FAU - Wang, Qian
AU  - Wang Q
AD  - ,.
FAU - Xu, Qiang
AU  - Xu Q
AD  - ,.
FAU - Li, Cui
AU  - Li C
AD  - ,.
FAU - Hu, Liting
AU  - Hu L
AD  - ,.
FAU - Peng, Xudong
AU  - Peng X
AD  - ,.
FAU - Yu, Feifei
AU  - Yu F
AD  - ,.
FAU - Xu, Ming
AU  - Xu M
AD  - ,.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Immunologic Factors)
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Aspergillosis/*immunology
MH  - Aspergillus fumigatus
MH  - Cell Polarity/*immunology
MH  - Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/metabolism
MH  - Immunologic Factors
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/*immunology
MH  - *Keratitis/immunology/microbiology
MH  - Macrophage Activation/drug effects/*immunology
MH  - Mice
MH  - Phagocytosis/*immunology
MH  - Signal Transduction/drug effects/physiology
MH  - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
PMC - PMC7425693
COIS- Disclosure: N. Jiang, None; L. Zhang, None; G. Zhao, None; J. Lin, None; Q. Wang, 
      None; Q. Xu, None; C. Li, None; L. Hu, None; X. Peng, None; F. Yu, None; M. Xu, 
      None
EDAT- 2020/07/22 06:00
MHDA- 2021/01/02 06:00
PMCR- 2020/07/21
CRDT- 2020/07/22 06:00
PHST- 2020/07/22 06:00 [entrez]
PHST- 2020/07/22 06:00 [pubmed]
PHST- 2021/01/02 06:00 [medline]
PHST- 2020/07/21 00:00 [pmc-release]
AID - 2770345 [pii]
AID - IOVS-19-28471 [pii]
AID - 10.1167/iovs.61.8.28 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2020 Jul 1;61(8):28. doi: 10.1167/iovs.61.8.28.