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Differential Activation of Human Monocytes and Lymphocytes by Distinct Strains of Trypanosoma cruzi.

Magalhães LM, Viana A, Chiari E, Galvão LM, Gollob KJ, Dutra WO - PLoS Negl Trop Dis (2015)

Bottom Line: It is known that these DTUs have different geographical distribution, as well as biological features.TcI and TcII are major DTUs found in patients from northern and southern Latin America, respectively.These results show that TcI and TcII have a distinct immunological impact on human cells during early infection, which might influence disease progression.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Biologia das Interações Celulares, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

ABSTRACT

Background: Trypanosoma cruzi strains are currently classified into six discrete typing units (DTUs) named TcI to VI. It is known that these DTUs have different geographical distribution, as well as biological features. TcI and TcII are major DTUs found in patients from northern and southern Latin America, respectively. Our hypothesis is that upon infection of human peripheral blood cells, Y strain (Tc II) and Col cl1.7 (Tc I), cause distinct immunological changes, which might influence the clinical course of Chagas disease.

Methodology/principal findings: We evaluated the infectivity of CFSE-stained trypomastigotes of Col cl1.7 and Y strain in human monocytes for 15 and 72 hours, and determined the immunological profile of lymphocytes and monocytes exposed to the different isolates using multiparameter flow cytometry. Our results showed a similar percentage and intensity of monocyte infection by Y and Col cl1.7. We also observed an increased expression of CD80 and CD86 by monocytes infected with Col cl1.7, but not Y strain. IL-10 was significantly higher in monocytes infected with Col cl1.7, as compared to Y strain. Moreover, infection with Col cl1.7, but not Y strain, led to an increased expression of IL-17 by CD8+ T cells. On the other hand, we observed a positive correlation between the expression of TNF-alpha and granzyme A only after infection with Y strain.

Conclusion/significance: Our study shows that while Col cl1.7 induces higher monocyte activation and, at the same time, production of IL-10, infection with Y strain leads to a lower monocyte activation but higher inflammatory profile. These results show that TcI and TcII have a distinct immunological impact on human cells during early infection, which might influence disease progression.

No MeSH data available.


Related in: MedlinePlus

Determination of the MFI of HLA-DR, TLR-2, CD80 and CD86 in human monocytes infected or not with strains of T. cruzi.Results are expressed as average ± standard deviation. The symbol * indicates p< 0.05 between groups. Determination of mean intensity of (A) HLA-DR in CFSE+ monocytes after 15 hours of culture; (B) HLA-DR in CFSE- monocytes after 15 hours of culture; (C) TLR-2 in CFSE+ monocytes after 15 hours of culture; (D) TLR-2 in CFSE- monocytes after 15 hours of culture; (E) CD80 in CFSE+ monocytes after 72 hours of culture; (F) CD80 in CFSE- monocytes after 72 hours of culture; (G) CD86 in CFSE+ monocytes after 72 hours of culture; (H) CD86 in CFSE- monocytes after 72 hours of culture. Histogram inserts show a representative overlay for the expression of each of the molecules under the different conditions.
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pntd.0003816.g002: Determination of the MFI of HLA-DR, TLR-2, CD80 and CD86 in human monocytes infected or not with strains of T. cruzi.Results are expressed as average ± standard deviation. The symbol * indicates p< 0.05 between groups. Determination of mean intensity of (A) HLA-DR in CFSE+ monocytes after 15 hours of culture; (B) HLA-DR in CFSE- monocytes after 15 hours of culture; (C) TLR-2 in CFSE+ monocytes after 15 hours of culture; (D) TLR-2 in CFSE- monocytes after 15 hours of culture; (E) CD80 in CFSE+ monocytes after 72 hours of culture; (F) CD80 in CFSE- monocytes after 72 hours of culture; (G) CD86 in CFSE+ monocytes after 72 hours of culture; (H) CD86 in CFSE- monocytes after 72 hours of culture. Histogram inserts show a representative overlay for the expression of each of the molecules under the different conditions.

Mentions: In order to access if there was a difference in monocyte activation after the infection with Y strain or Col cl1.7, we analyzed the expression of HLA-DR and TLR-2. HLA-DR is an important antigen-presenting molecule whose expression changes upon activation [21]. It is known that activation of TLR-2 is involved with activation of Rab-5, fusion with endosomes and phagocytosis of the trypomastigote form [22]. Since these changes occur early after activation, we evaluated the expression of HLA-DR and TLR-2 after 15 hours of infection. Our results show that monocytes infected with either T. cruzi strain (CD14+CFSE+ cells) express higher intensity of HLA-DR and TLR-2 compared with media control (Fig 2A and 2C). On the other hand, non-infected monocytes (CD14+CFSE- cells) did not show significant changes in the intensity of expression of these molecules as compared to media control (Fig 2B and 2D).


Differential Activation of Human Monocytes and Lymphocytes by Distinct Strains of Trypanosoma cruzi.

Magalhães LM, Viana A, Chiari E, Galvão LM, Gollob KJ, Dutra WO - PLoS Negl Trop Dis (2015)

Determination of the MFI of HLA-DR, TLR-2, CD80 and CD86 in human monocytes infected or not with strains of T. cruzi.Results are expressed as average ± standard deviation. The symbol * indicates p< 0.05 between groups. Determination of mean intensity of (A) HLA-DR in CFSE+ monocytes after 15 hours of culture; (B) HLA-DR in CFSE- monocytes after 15 hours of culture; (C) TLR-2 in CFSE+ monocytes after 15 hours of culture; (D) TLR-2 in CFSE- monocytes after 15 hours of culture; (E) CD80 in CFSE+ monocytes after 72 hours of culture; (F) CD80 in CFSE- monocytes after 72 hours of culture; (G) CD86 in CFSE+ monocytes after 72 hours of culture; (H) CD86 in CFSE- monocytes after 72 hours of culture. Histogram inserts show a representative overlay for the expression of each of the molecules under the different conditions.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492932&req=5

pntd.0003816.g002: Determination of the MFI of HLA-DR, TLR-2, CD80 and CD86 in human monocytes infected or not with strains of T. cruzi.Results are expressed as average ± standard deviation. The symbol * indicates p< 0.05 between groups. Determination of mean intensity of (A) HLA-DR in CFSE+ monocytes after 15 hours of culture; (B) HLA-DR in CFSE- monocytes after 15 hours of culture; (C) TLR-2 in CFSE+ monocytes after 15 hours of culture; (D) TLR-2 in CFSE- monocytes after 15 hours of culture; (E) CD80 in CFSE+ monocytes after 72 hours of culture; (F) CD80 in CFSE- monocytes after 72 hours of culture; (G) CD86 in CFSE+ monocytes after 72 hours of culture; (H) CD86 in CFSE- monocytes after 72 hours of culture. Histogram inserts show a representative overlay for the expression of each of the molecules under the different conditions.
Mentions: In order to access if there was a difference in monocyte activation after the infection with Y strain or Col cl1.7, we analyzed the expression of HLA-DR and TLR-2. HLA-DR is an important antigen-presenting molecule whose expression changes upon activation [21]. It is known that activation of TLR-2 is involved with activation of Rab-5, fusion with endosomes and phagocytosis of the trypomastigote form [22]. Since these changes occur early after activation, we evaluated the expression of HLA-DR and TLR-2 after 15 hours of infection. Our results show that monocytes infected with either T. cruzi strain (CD14+CFSE+ cells) express higher intensity of HLA-DR and TLR-2 compared with media control (Fig 2A and 2C). On the other hand, non-infected monocytes (CD14+CFSE- cells) did not show significant changes in the intensity of expression of these molecules as compared to media control (Fig 2B and 2D).

Bottom Line: It is known that these DTUs have different geographical distribution, as well as biological features.TcI and TcII are major DTUs found in patients from northern and southern Latin America, respectively.These results show that TcI and TcII have a distinct immunological impact on human cells during early infection, which might influence disease progression.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Biologia das Interações Celulares, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

ABSTRACT

Background: Trypanosoma cruzi strains are currently classified into six discrete typing units (DTUs) named TcI to VI. It is known that these DTUs have different geographical distribution, as well as biological features. TcI and TcII are major DTUs found in patients from northern and southern Latin America, respectively. Our hypothesis is that upon infection of human peripheral blood cells, Y strain (Tc II) and Col cl1.7 (Tc I), cause distinct immunological changes, which might influence the clinical course of Chagas disease.

Methodology/principal findings: We evaluated the infectivity of CFSE-stained trypomastigotes of Col cl1.7 and Y strain in human monocytes for 15 and 72 hours, and determined the immunological profile of lymphocytes and monocytes exposed to the different isolates using multiparameter flow cytometry. Our results showed a similar percentage and intensity of monocyte infection by Y and Col cl1.7. We also observed an increased expression of CD80 and CD86 by monocytes infected with Col cl1.7, but not Y strain. IL-10 was significantly higher in monocytes infected with Col cl1.7, as compared to Y strain. Moreover, infection with Col cl1.7, but not Y strain, led to an increased expression of IL-17 by CD8+ T cells. On the other hand, we observed a positive correlation between the expression of TNF-alpha and granzyme A only after infection with Y strain.

Conclusion/significance: Our study shows that while Col cl1.7 induces higher monocyte activation and, at the same time, production of IL-10, infection with Y strain leads to a lower monocyte activation but higher inflammatory profile. These results show that TcI and TcII have a distinct immunological impact on human cells during early infection, which might influence disease progression.

No MeSH data available.


Related in: MedlinePlus