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

Costa, Germano C.; Rocha, Manoel Otávio da Costa; Souza, Paulo Eduardo Alencar; Melo, D; Moreira, Paula Rocha; Gollob, Kenneth J.; Nunes, Maria do Carmo Pereira; Dutra, Walderez Ornelas

doi:10.1590/0074-02760200110

Cited by 3 publications

(3 citation statements)

References 16 publications

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“…The CD14 receptor encoded by the CD14 gene is a leucine-rich receptor mainly expressed on the surface of natural cells, especially monocytes/macrophages. It can also act as a receptor in a soluble form (sCD14) on cells that do not express CD14 on their surface, such as dendritic cells ( 24 ). It plays an important protective role as a pattern recognition molecule to recognize a variety of inflammatory mediators ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

Dysregulation and imbalance of innate and adaptive immunity are involved in the cardiomyopathy progression

Quan

Cai

et al. 2022

Front. Cardiovasc. Med.

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BackgroundCardiomyopathy is known to be a heterogeneous disease with numerous etiologies. They all have varying degrees and types of myocardial pathological changes, resulting in impaired contractility, ventricle relaxation, and heart failure. The purpose of this study was to determine the pathogenesis, immune-related pathways and important biomarkers engaged in the progression of cardiomyopathy from various etiologies.MethodsWe downloaded the gene microarray data from the Gene Expression Omnibus (GEO). The hub genes between cardiomyopathy and non-cardiomyopathy control groups were identified using differential expression analysis, least absolute shrinkage and selection operator (LASSO) regression and weighted gene co-expression network analysis (WGCNA). To assess the diagnostic precision of hub genes, receiver-operating characteristic (ROC) curves as well as the area under the ROC curve (AUC) were utilized. Then, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis and Gene Ontology (GO) analysis were conducted on the obtained differential genes. Finally, single-sample GSEA (ssGSEA) and Gene Set Enrichment Analysis (GSEA) were utilized to analyze the infiltration level of 28 immune cells and their relationship with hub genes based on gene expression profile data and all differential gene files.ResultsA total of 82 differentially expressed genes (DEGs) were screened after the training datasets were merged and intersected. The WGCNA analysis clustered the expression profile data into four co-expression modules, The turquoise module exhibited the strongest relationship with clinical traits, and nine candidate key genes were obtained from the module. Then we intersected DEGs with nine candidate genes. LASSO regression analysis identified the last three hub genes as promising biomarkers to distinguish the cardiomyopathy group from the non-cardiomyopathy control group. ROC curve analysis in the validation dataset revealed the sensitivity and accuracy of three hub genes as marker genes. The majority of the functional enrichment analysis results were concentrated on immunological and inflammatory pathways. Immune infiltration analysis revealed a significant correlation between regulatory T cells, type I helper T cells, macrophages, myeloid-derived suppressor cells, natural killer cells, activated dendritic cells and the abundance of immune infiltration in hub genes.ConclusionThe hub genes (CD14, CCL2, and SERPINA3) can be used as markers to distinguish cardiomyopathy from non-cardiomyopathy individuals. Among them, SERPINA3 has the best diagnostic performance. T cell immunity (adaptive immune response) is closely linked to cardiomyopathy progression. Hub genes may protect the myocardium from injury through myeloid-derived suppressor cells, regulatory T cells, helper T cells, monocytes/macrophages, natural killer cells and activated dendritic cells. The innate immune response is crucial to this process. Dysregulation and imbalance of innate immune cells or activation of adaptive immune responses are involved in cardiomyopathy disease progression in patients.

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Section: Discussionmentioning

confidence: 99%

Dysregulation and imbalance of innate and adaptive immunity are involved in the cardiomyopathy progression

Quan

Cai

et al. 2022

Front. Cardiovasc. Med.

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“…CD14 has also been identified as a potential mediator of amyotrophic lateral sclerosis (AMLS) [78] and strategies for CD14 neutralization for AMLS treatment are being pursued. A more general role of CD14 in autoimmune conditions is supported by its elevated levels in patients with systemic sclerosis [79], psoriasis [80], Kawasaki's disease [81], acute pancreatitis [82], osteoarthritis [59], vasculitis [83], and primary biliary cholangitis [84].…”

Section: Cd14 In Human Diseasesmentioning

confidence: 99%

Role of CD14 in human disease

et al. 2023

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The cell surface antigen CD14 is primarily understood to act as a co-receptor for toll-like receptors (TLRs) to activate innate immunity responses to pathogens and tissue injury in macrophages and monocytes. However, roles for CD14 are increasingly being uncovered in disease responses in epithelial and endothelial cells. Consistent with these broader functions, CD14 expression is altered in a variety of non-immune cell types in response to a several of disease states. Moreover, soluble CD14 activated by factors from both pathogens and tissue damage may initiate signalling in a variety of non-immune cells. This review examined the current understanding CD14 in innate immunity as well as its potential functions in nonimmune cells and associated human diseases.

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“… 60 , 61 In the same line, an association between a CD14 genotype and the development of Chagas dilated cardiomyopathy was established. 62 On the other hand, the protective role of IL17A AA, IL18 AA, and IL1B TC genotypes against development/progression of cardiomyopathy has been reported. 63 …”

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confidence: 99%

Trypanosoma cruzi genetic diversity: impact on transmission cycles and Chagas disease

Zingales

Bartholomeu

2022

Mem. Inst. Oswaldo Cruz

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Trypanosoma cruzi , the agent of Chagas disease (ChD), exhibits remarkable biological and genetic diversity, along with eco-epidemiological complexity. In order to facilitate communication among researchers aiming at the characterisation of biological and epidemiological aspects of T. cruzi , parasite isolates and strains were partitioned into seven discrete typing units (DTUs), TcI-TcVI and TcBat, identifiable by reproducible genotyping protocols. Here we present the potential origin of the genetic diversity of T. cruzi and summarise knowledge about eco-epidemiological associations of DTUs with mammalian reservoirs and vectors. Circumstantial evidence of a connection between T. cruzi genotype and ChD manifestations is also discussed emphasising the role of the host’s immune response in clinical ChD progression. We describe genomic aspects of DTUs focusing on polymorphisms in multigene families encoding surface antigens that play essential functions for parasite survival both in the insect vector and the mammalian host. Such antigens most probably contributed to the parasite success in establishing infections in different hosts and exploring several niches. Gaps in the current knowledge and challenges for future research are pointed out.

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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

Cited by 3 publications

References 16 publications

Dysregulation and imbalance of innate and adaptive immunity are involved in the cardiomyopathy progression

Dysregulation and imbalance of innate and adaptive immunity are involved in the cardiomyopathy progression

Role of CD14 in human disease

Trypanosoma cruzi genetic diversity: impact on transmission cycles and Chagas disease

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