Regulatory T cells and IgE expression in duodenal mucosa of Strongyloides stercoralis and human T lymphotropic virus type 1 co-infected patients.
Adolescent
Adult
Biopsy
Coinfection
/ complications
Duodenum
/ pathology
Female
Gene Expression
HTLV-I Infections
/ complications
Humans
Immunoglobulin E
/ analysis
Immunohistochemistry
Immunologic Factors
/ analysis
Intestinal Mucosa
/ pathology
Male
Middle Aged
Strongyloidiasis
/ complications
T-Lymphocytes, Regulatory
/ immunology
Young Adult
Journal
PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
06
08
2018
accepted:
28
04
2019
revised:
18
06
2019
pubmed:
7
6
2019
medline:
28
11
2019
entrez:
7
6
2019
Statut:
epublish
Résumé
Strongyloides stercoralis is an intestinal nematode unique in its ability to replicate in the human host, allowing ongoing cycles of autoinfection, persisting for decades within the same host. Although usually asymptomatic, overwhelming infections can occur in Strongyloides and HTLV-1 co-infected individuals (SS/HTLV-1). Regulatory T cells (Tregs) are able to blunt specific Th2 responses necessary to control the parasite. We previously reported that peripheral blood Tregs are increased in SS/HTLV-1 and correlate with low Th2 responses. We hypothesized that Tregs are also increased at the site of infection in duodenal mucosa. Paraffin embedded duodenal biopsies were obtained from 10 SS/HTLV-1 patients, 3 controls with non-parasitic chronic duodenitis, and 2 healthy controls. Immunohistochemistry was performed using monoclonal antibodies against human CD3, CD8, IgE and FoxP3. The number of cells were counted using a conventional light microscope. The number of CD3+, CD8+, FoxP3+ and IgE positive cells per 0.35 mm2 was measured using ImagePro Plus software comparing areas adjacent or distant from parasite material. In patients with SS/HTLV-1, T lymphocyte counts and CD8+ cells were lower in areas adjacent to the parasite compared to non-adjacent areas (CD3+: adjacent: 6.5 [Interquartile range (IQR: 2.8-12.3)]; non-adjacent: 24.5 [IQR: 20.9-34.4]; Mann-Whitney p = 0.0003; CD8+: adjacent: 4.5 [IQR: 2.3-11.8]; non-adjacent: 21 [IQR: 15.3-42.9]; Mann-Whitney p = 0.0011). Tregs cells in the intestines (FoxP3+ expressing cells) were increased in patients with SS/HTLV-1 compared with patients with chronic duodenitis (SS/HTLV-1: 1.5 [IQR: 0.7-2.3]; duodenitis controls: 0 [range 0-0.7]; healthy controls: 0; Mann-Whitney p = 0.034). There was also a trend towards fewer eosinophils adjacent to the parasites. Among SS/HTLV-1 patients the number of IgE expressing cells was increased for in areas not adjacent to the parasite compared to non-adjacent areas (ANOVA, p = 0.001). Our data shows increased Treg cell numbers localized adjacent to the parasites in the duodenum SS/HTLV-1 patients. In addition, other T lymphocytes and IgE expressing cells were decreased adjacent to the parasites, suggesting an important role for Tregs in down-regulating local parasite effector responses.
Sections du résumé
BACKGROUND
Strongyloides stercoralis is an intestinal nematode unique in its ability to replicate in the human host, allowing ongoing cycles of autoinfection, persisting for decades within the same host. Although usually asymptomatic, overwhelming infections can occur in Strongyloides and HTLV-1 co-infected individuals (SS/HTLV-1). Regulatory T cells (Tregs) are able to blunt specific Th2 responses necessary to control the parasite. We previously reported that peripheral blood Tregs are increased in SS/HTLV-1 and correlate with low Th2 responses. We hypothesized that Tregs are also increased at the site of infection in duodenal mucosa.
METHODS
Paraffin embedded duodenal biopsies were obtained from 10 SS/HTLV-1 patients, 3 controls with non-parasitic chronic duodenitis, and 2 healthy controls. Immunohistochemistry was performed using monoclonal antibodies against human CD3, CD8, IgE and FoxP3. The number of cells were counted using a conventional light microscope. The number of CD3+, CD8+, FoxP3+ and IgE positive cells per 0.35 mm2 was measured using ImagePro Plus software comparing areas adjacent or distant from parasite material.
RESULTS
In patients with SS/HTLV-1, T lymphocyte counts and CD8+ cells were lower in areas adjacent to the parasite compared to non-adjacent areas (CD3+: adjacent: 6.5 [Interquartile range (IQR: 2.8-12.3)]; non-adjacent: 24.5 [IQR: 20.9-34.4]; Mann-Whitney p = 0.0003; CD8+: adjacent: 4.5 [IQR: 2.3-11.8]; non-adjacent: 21 [IQR: 15.3-42.9]; Mann-Whitney p = 0.0011). Tregs cells in the intestines (FoxP3+ expressing cells) were increased in patients with SS/HTLV-1 compared with patients with chronic duodenitis (SS/HTLV-1: 1.5 [IQR: 0.7-2.3]; duodenitis controls: 0 [range 0-0.7]; healthy controls: 0; Mann-Whitney p = 0.034). There was also a trend towards fewer eosinophils adjacent to the parasites. Among SS/HTLV-1 patients the number of IgE expressing cells was increased for in areas not adjacent to the parasite compared to non-adjacent areas (ANOVA, p = 0.001).
CONCLUSIONS
Our data shows increased Treg cell numbers localized adjacent to the parasites in the duodenum SS/HTLV-1 patients. In addition, other T lymphocytes and IgE expressing cells were decreased adjacent to the parasites, suggesting an important role for Tregs in down-regulating local parasite effector responses.
Identifiants
pubmed: 31170141
doi: 10.1371/journal.pntd.0007415
pii: PNTD-D-18-01196
pmc: PMC6581271
doi:
Substances chimiques
Immunologic Factors
0
Immunoglobulin E
37341-29-0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0007415Subventions
Organisme : NIAID NIH HHS
ID : R01 AI136870
Pays : United States
Organisme : FIC NIH HHS
ID : R01 TW007642
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Parasitol Int. 2017 Feb;66(1):807-812
pubmed: 27744050
PLoS Negl Trop Dis. 2013 Jul 11;7(7):e2288
pubmed: 23875033
PLoS Negl Trop Dis. 2009 Jun 09;3(6):e456
pubmed: 19513105
West Indian Med J. 2004 Jan;53(1):3-6
pubmed: 15114885
J Clin Pathol. 1996 Sep;49(9):717-20
pubmed: 9038754
J Immunol. 2000 Oct 15;165(8):4544-51
pubmed: 11035095
Immunol Res. 2011 Dec;51(2-3):205-14
pubmed: 22101674
Epidemiol Infect. 2015 Feb;143(3):452-60
pubmed: 24990510
PLoS Pathog. 2013;9(4):e1003263
pubmed: 23592987
PLoS Negl Trop Dis. 2013 May 09;7(5):e2214
pubmed: 23675546
Infect Immun. 2015 Nov 23;84(2):425-31
pubmed: 26597982
Parasite Immunol. 2006 Aug;28(8):397-400
pubmed: 16879311
Parasitology. 2017 Mar;144(3):295-315
pubmed: 26905057
Infect Immun. 2006 Oct;74(10):5730-8
pubmed: 16988250
Lancet Infect Dis. 2007 Apr;7(4):266-81
pubmed: 17376384
PLoS Pathog. 2014 Feb 06;10(2):e1003913
pubmed: 24516385
Adv Parasitol. 2015 Apr;88:165-241
pubmed: 25911368
Int J Infect Dis. 2002 Mar;6(1):28-30
pubmed: 12044298
Pathog Glob Health. 2013 Jun;107(4):202-6
pubmed: 23816512
Oncogene. 2000 Oct 12;19(43):4954-60
pubmed: 11042682
Parasite Immunol. 2004 Nov-Dec;26(11-12):487-97
pubmed: 15771684
Parasitology. 2017 Mar;144(3):263-273
pubmed: 27181117
Curr Opin Infect Dis. 2010 Oct;23(5):500-4
pubmed: 20733481
Rev Soc Bras Med Trop. 2013 Mar-Apr;46(2):241-3
pubmed: 23740053
Infect Immun. 2011 Jul;79(7):2770-8
pubmed: 21482685
Parasite Immunol. 2001 Sep;23(9):503-7
pubmed: 11589779
J Immunol. 2011 Apr 1;186(7):4295-305
pubmed: 21335490
PLoS Negl Trop Dis. 2013 May 09;7(5):e2165
pubmed: 23675541
Rev Panam Salud Publica. 2007 Oct;22(4):223-30
pubmed: 18078583