Toward a humanized mouse model of Pneumocystis pneumonia.
Animals
Antibodies, Fungal
/ biosynthesis
Antigens, CD34
/ metabolism
Cell Adhesion Molecules
/ genetics
Disease Models, Animal
Female
Gene Expression
Hematopoietic Stem Cell Transplantation
Heterografts
Host Microbial Interactions
/ genetics
Host Specificity
/ immunology
Humans
Immunoglobulin G
/ biosynthesis
Immunoglobulin M
/ biosynthesis
Lectins, C-Type
/ genetics
Lung
/ immunology
Mice
Mice, Transgenic
Pneumocystis
/ immunology
Pneumonia, Pneumocystis
/ genetics
Receptors, Cell Surface
/ genetics
Species Specificity
Cytokines
Fungal infections
Infectious disease
Pulmonology
Journal
JCI insight
ISSN: 2379-3708
Titre abrégé: JCI Insight
Pays: United States
ID NLM: 101676073
Informations de publication
Date de publication:
25 01 2021
25 01 2021
Historique:
received:
27
04
2020
accepted:
09
12
2020
entrez:
25
1
2021
pubmed:
26
1
2021
medline:
5
6
2021
Statut:
epublish
Résumé
Pneumocystis is an important opportunistic fungus that causes pneumonia in children and immunocompromised individuals. Recent genomic data show that divergence of major surface glycoproteins may confer speciation and host range selectivity. On the other hand, immune clearance between mice and humans is well correlated. Thus, we hypothesized that humanize mice may provide information about human immune responses involved in controlling Pneumocystis infection. CD34-engrafted huNOG-EXL mice controlled fungal burdens to a greater extent than nonengrafted mice. Moreover, engrafted mice generated fungal-specific IgM. Fungal control was associated with a transcriptional signature that was enriched for genes associated with nonopsonic recognition of trophs (CD209) and asci (CLEC7A). These same genes were downregulated in CD4-deficient mice as well as twins with bare lymphocyte syndrome with Pneumocystis pneumonia.
Identifiants
pubmed: 33491669
pii: 139573
doi: 10.1172/jci.insight.139573
pmc: PMC7934868
doi:
pii:
Substances chimiques
Antibodies, Fungal
0
Antigens, CD34
0
Cell Adhesion Molecules
0
DC-specific ICAM-3 grabbing nonintegrin
0
Immunoglobulin G
0
Immunoglobulin M
0
Lectins, C-Type
0
Receptors, Cell Surface
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI120033
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL139930
Pays : United States
Références
Cell. 2015 Oct 8;163(2):367-80
pubmed: 26411289
Clin Respir J. 2018 Jan;12(1):16-22
pubmed: 26878193
mSphere. 2019 Sep 4;4(5):
pubmed: 31484742
N Engl J Med. 1977 Dec 22;297(25):1381-3
pubmed: 337137
Infect Immun. 2017 Mar 23;85(4):
pubmed: 28031260
J Infect Dis. 2000 Jun;181(6):2011-7
pubmed: 10837183
J Exp Med. 2003 Dec 1;198(11):1677-88
pubmed: 14657220
Pathogens. 2019 Mar 12;8(1):
pubmed: 30871027
Enferm Infecc Microbiol Clin. 2020 Mar;38(3):111-118
pubmed: 31272810
Infect Immun. 2014 Jun;82(6):2417-23
pubmed: 24686066
JCI Insight. 2018 Jun 21;3(12):
pubmed: 29925696
J Immunol. 2013 Jan 1;190(1):285-95
pubmed: 23203926
Am J Respir Crit Care Med. 1995 Apr;151(4):1233-8
pubmed: 7697258
PLoS One. 2010 Jan 29;5(1):e8524
pubmed: 20126455
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
J Clin Microbiol. 1995 Mar;33(3):718-24
pubmed: 7751383
Nat Immunol. 2011 Jun 12;12(7):639-46
pubmed: 21666689
Cell Rep. 2017 Mar 28;18(13):3078-3090
pubmed: 28355561
Dev Period Med. 2019;23(3):159-162
pubmed: 31654993
Infect Immun. 2006 Apr;74(4):2446-8
pubmed: 16552076
J Immunol. 2015 Jul 1;195(1):185-93
pubmed: 25994969