CD14 genotype and functional dichotomy of CD14+ and CD14- cells are associated with activated immune response and development of Chagas dilated cardiomyopathy

We aimed to investigate the association of CD14 -260C/T (rs2569190) polymorphism and Chagas cardiomyopathy and the functional characteristics of CD14+ and CD14- monocytes upon infection with Trypanosoma cruzi. We observed an association between the T- genotype (absence of allele -260T) related to low CD14 expression and the dilated cardiomyopathy type of Chagas disease. Furthermore, we observed that CD14- monocytes showed a more activated profile upon in vitro infection with T. cruzi than CD14+ monocytes. Our findings suggest that T- genotype is associated with susceptibility to develop Chagas dilated cardiomyopathy, likely linked to the T. cruzi-induced inflammatory profile of CD14- monocytes.

Key words:
Chagas cardiomyopathy; CD14; polymorphism

Authorship

Germano Carneiro Costa ⁺+ Corresponding author: germanocarneiro@gmail.com

Universidade Federal de Viçosa, Florestal, MG, BrasilUniversidade Federal de ViçosaBrazilFlorestal, MG, BrazilUniversidade Federal de Viçosa, Florestal, MG, Brasil

http://orcid.org/0000-0003-3711-5840

Manoel Otávio da Costa Rocha

Universidade Federal de Minas Gerais, Faculdade de Medicina, Programa de Pós-Graduação em Infectologia e Medicina Tropical, Belo Horizonte, MG, BrasilUniversidade Federal de Minas GeraisBrazilBelo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais, Faculdade de Medicina, Programa de Pós-Graduação em Infectologia e Medicina Tropical, Belo Horizonte, MG, Brasil

Paulo Eduardo Alencar de Souza

Pontifícia Universidade Católica de Minas Gerais, Faculdade de Odontologia, Belo Horizonte, MG, Brasil Pontifícia Universidade Católica de Minas GeraisBrazilBelo Horizonte, MG, BrazilPontifícia Universidade Católica de Minas Gerais, Faculdade de Odontologia, Belo Horizonte, MG, Brasil

Diego Felipe SA Melo

Universidade Federal de Minas Gerais, Departamento de Morfologia, Laboratório de Biologia das Interações Celulares, Belo Horizonte, MG, BrasilUniversidade Federal de Minas GeraisBrazilBelo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais, Departamento de Morfologia, Laboratório de Biologia das Interações Celulares, Belo Horizonte, MG, Brasil

Paula Rocha Moreira

Kenneth John Gollob

AC Camargo Cancer Center, São Paulo, SP, Brasil AC Camargo Cancer CenterBrazilSão Paulo, SP, BrazilAC Camargo Cancer Center, São Paulo, SP, Brasil

Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais, Salvador, BA, BrasilInstituto Nacional de Ciência e Tecnologia de Doenças TropicaisBrasilSalvador, BA, BrasilInstituto Nacional de Ciência e Tecnologia de Doenças Tropicais, Salvador, BA, Brasil

Maria do Carmo Pereira Nunes

Walderez Ornelas Dutra

+ Corresponding author: germanocarneiro@gmail.com

GCC: main author in charge of practical experiments, analysis and writing of the manuscript. MOCR and MCPN: medical doctors responsible for caring for patients involved in this study. PEAS: assistant in phenotypical experiments and analysis involving adherent cells protocol. DFSAM: assistant in genotype experiments. PRM: assistant in genotype experiments and analysis. KJG: co-advisor, developed the project design and assisted in analysis of results. WOD: main advisor, developed the project design and assisted in all stages of practical implementing, analysis of results and writing of the manuscript.

SCIMAGO INSTITUTIONS RANKINGS

Universidade Federal de Viçosa, Florestal, MG, BrasilUniversidade Federal de ViçosaBrazilFlorestal, MG, BrazilUniversidade Federal de Viçosa, Florestal, MG, Brasil

AC Camargo Cancer Center, São Paulo, SP, Brasil AC Camargo Cancer CenterBrazilSão Paulo, SP, BrazilAC Camargo Cancer Center, São Paulo, SP, Brasil

Figures | Tables

Figures (1)
Tables (1)

Thumbnail

Determination of infectivity and functional analysis of CD14+ and CD14- cells. (A) Density plot shows the selection of CD14+ and CD14- cells using side-scatter vs CD14 expression plot, in which the expression of CFSE was evaluated. Results are expressed as the mean intensity of CFSE expression and percentage of CFSE+ cells. (B) Analysis of CD80 and CD86 mean intensity of expression by CD14+ and CD14- cells non-stimulated (medium treated cells) and after in vitro infection with T. cruzi trypomastigotes. Results are presented as mean ± standard deviation (SD). (C) Analysis of IL-10 and TNF-alpha mean intensity of expression by non-stimulated CD14+ and CD14- cells (medium treated cells) and after in vitro infection with T. cruzi trypomastigotes. Results are presented as mean ± SD. (D) Analysis of IL-10/TNF ratio in CD14- and CD14+ cells. Statistically significant results were obtained using the Wilcoxon paired test (p < 0.05) for comparisons of different cell populations or different treatment groups.

Thumbnail

TABLE
Demographic characteristics and genotype and allele frequency of the CD14 -260 C/T polymorphisms in Chagas disease patients

Determination of infectivity and functional analysis of CD14+ and CD14- cells. (A) Density plot shows the selection of CD14+ and CD14- cells using side-scatter vs CD14 expression plot, in which the expression of CFSE was evaluated. Results are expressed as the mean intensity of CFSE expression and percentage of CFSE+ cells. (B) Analysis of CD80 and CD86 mean intensity of expression by CD14+ and CD14- cells non-stimulated (medium treated cells) and after in vitro infection with T. cruzi trypomastigotes. Results are presented as mean ± standard deviation (SD). (C) Analysis of IL-10 and TNF-alpha mean intensity of expression by non-stimulated CD14+ and CD14- cells (medium treated cells) and after in vitro infection with T. cruzi trypomastigotes. Results are presented as mean ± SD. (D) Analysis of IL-10/TNF ratio in CD14- and CD14+ cells. Statistically significant results were obtained using the Wilcoxon paired test (p < 0.05) for comparisons of different cell populations or different treatment groups.

TABLE Demographic characteristics and genotype and allele frequency of the CD14 -260 C/T polymorphisms in Chagas disease patients

	Clinical groups
	Indeterminate (n = 64)	Non-dilated cardiac (n = 53)	Dilated cardiac (n = 68)
Gender
Male	29 (45.0)	22 (41.5)	41 (60.0)
Female	35 (55.0)	31 (58.5)	27 (40.0)
Age range
Range	18-73	29-67	22-73
Mean ± SD	43.3±10.4	46.6±9.4	50.86±11.2
LVEF (%)	65.6±5.05	62.5±5.6	43.35±11.86
Genotype
CC	17 (26.5)	21 (40.0)	29 (43.0)
CT	34 (53.0)	25 (47.0)	28 (41.0)
TT	13 (20.5)	7 (13.0)	11 (16.0)
T^-a	17 (26.5)	21 (39.6)	29 (42.6)
T^+a	47 (73.5)	32 (60.4)	39 (57.4)
Allele
C	68 (53.0)	67 (63.0)	86 (63.0)
T	60 (47.0)	39 (37.0)	50 (37.0)

Data is shown as number (%) of subjects. χ² likelihood test were used for 3 × 2 contingency table comparison among different clinical groups, degrees of freedom (df) = 2. Fisher exact test were used for 2 × 2 contingency table (comparison used for allele T carriage and allele frequency). a: dilated cardiac (DC) × indeterminate (IND): χ² = 3.79, p = 0.05; odds ratio: 2.05 (95%CI 0.97-4.28); LVEF: left ventricular ejection fraction; SD: standard deviation.

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CD14 genotype and functional dichotomy of CD14+ and CD14- cells are associated with activated immune response and development of Chagas dilated cardiomyopathy

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[1] + Corresponding author: germanocarneiro@gmail.com