PMID- 23836814
OWN - NLM
STAT- MEDLINE
DCOM- 20140220
LR  - 20211021
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 81
IP  - 9
DP  - 2013 Sep
TI  - Dectin immunoadhesins and pneumocystis pneumonia.
PG  - 3451-62
LID - 10.1128/IAI.00136-13 [doi]
AB  - The opportunistic pathogen Pneumocystis jirovecii is a significant cause of 
      disease in HIV-infected patients and others with immunosuppressive conditions. 
      Pneumocystis can also cause complications in treatment following antiretroviral 
      therapy or reversal of immunosuppressive therapy, as the newly reconstituted 
      immune system can develop a pathological inflammatory response to remaining 
      antigens or a previously undetected infection. To target beta-(1,3)-glucan, a 
      structural component of the Pneumocystis cell wall with immune-stimulating 
      properties, we have developed immunoadhesins consisting of the carbohydrate 
      binding domain of Dectin-1 fused to the Fc regions of the 4 subtypes of murine 
      IgG (mIgG). These immunoadhesins bind beta-glucan with high affinity, and precoating 
      the surface of zymosan with Dectin-1:Fc can reduce cytokine production by 
      macrophages in an in vitro stimulation assay. All Dectin-1:Fc variants showed 
      specificity of binding to the asci of Pneumocystis murina, but effector activity 
      of the fusion molecules varied depending on Fc subtype. Dectin-1:mIgG2a Fc was 
      able to reduce the viability of P. murina in culture through a 
      complement-dependent mechanism, whereas previous studies have shown the mIgG1 Fc 
      fusion to increase macrophage-dependent killing. In an in vivo challenge model, 
      systemic expression of Dectin-1:mIgG1 Fc significantly reduced ascus burden in 
      the lung. When administered postinfection in a model of immune reconstitution 
      inflammatory syndrome (IRIS), both Dectin-1:mIgG1 and Dectin-1:mIgG2a Fc reduced 
      hypoxemia despite minimal effects on fungal burden in the lung. Taken together, 
      these data indicate that molecules targeting beta-glucan may provide a mechanism for 
      treatment of fungal infection and for modulation of the inflammatory response to 
      Pneumocystis and other pathogens.
FAU - Ricks, David M
AU  - Ricks DM
AD  - Department of Genetics, Louisiana State University Health Sciences Center, New 
      Orleans, Louisiana, USA.
FAU - Chen, Kong
AU  - Chen K
FAU - Zheng, Mingquan
AU  - Zheng M
FAU - Steele, Chad
AU  - Steele C
FAU - Kolls, Jay K
AU  - Kolls JK
LA  - eng
GR  - R01 HL062052/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20130708
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Cytokines)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Lectins, C-Type)
RN  - 0 (beta-Glucans)
RN  - 0 (dectin 1)
RN  - 9010-72-4 (Zymosan)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*immunology
MH  - B-Lymphocytes/immunology
MH  - Cell Wall/immunology
MH  - Cytokines/immunology
MH  - Immune Reconstitution Inflammatory Syndrome/immunology
MH  - Immunoglobulin G/immunology
MH  - Inflammation/immunology
MH  - Lectins, C-Type/*immunology
MH  - Lung/immunology
MH  - Macrophages/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pneumonia, Pneumocystis/*immunology
MH  - T-Lymphocytes/immunology
MH  - Zymosan/immunology
MH  - beta-Glucans/immunology
PMC - PMC3754224
EDAT- 2013/07/10 06:00
MHDA- 2014/02/22 06:00
PMCR- 2014/03/01
CRDT- 2013/07/10 06:00
PHST- 2013/07/10 06:00 [entrez]
PHST- 2013/07/10 06:00 [pubmed]
PHST- 2014/02/22 06:00 [medline]
PHST- 2014/03/01 00:00 [pmc-release]
AID - IAI.00136-13 [pii]
AID - 00136-13 [pii]
AID - 10.1128/IAI.00136-13 [doi]
PST - ppublish
SO  - Infect Immun. 2013 Sep;81(9):3451-62. doi: 10.1128/IAI.00136-13. Epub 2013 Jul 8.