Molecular Insights into Cell-Mediated Immunity in Atypical Non-Ulcerated Cutaneous Leishmaniasis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Sampling
2.2. Immunological and Molecular Diagnosis
2.3. Steps of RNA Sequencing, Differential Expression and Functional Enrichment Analysis
2.4. Comparison of Biomarkers of Immune Response Profiles and Lymphocyte Exhaustion
2.5. Immunohistochemistry Study
3. Results
3.1. RNAseq Analysis and Number of Differentially Expressed Genes (DEGs)
3.2. Identifying Gene Signature of Cell-Mediated Immunity in NUCL
3.3. Pathways Enrichment Analysis
3.4. Comparison of DEGs for CMI Between NUCL and VL
3.5. Blood Gene Expression Shows a Stronger Pro-Inflammatory Response and Regulation in NUCL than in VL
3.6. In Vivo Cell-Mediated Immunity Confirms a Stronger Pro-Inflammatory Response in NUCL
3.7. In Situ Cutaneous Evaluation Corroborates That NUCL Immune Response Is Predominantly Pro-Inflammatory
4. Discussion
4.1. T Lymphocyte Exhaustion
4.2. Innate IMMUNE Response
4.3. CD8+ T Lymphocytes
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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CMI DEG | LogFCAS | LogFCVL | LogFCNEG | Function |
---|---|---|---|---|
BATF2 | 1.25 | NS | NS | Enhances CD8+ T-cell infiltration and activation. |
SH3PXD2B | 1.15 | −1.77 | 4.49 | Allows NOX1- or NOX3-dependent reactive oxygen species (ROS) generation. |
CD274 | 1.10 | NS | 0.99 | Ligand for the inhibitory receptor PDCD1/PD-1. |
GBP1 | 0.84 | −1.41 | NS | Inflammasome assembly in response to infection. |
CCR3 | 0.83 | 5.92 | 1.89 | Receptor for C-C type chemokine. |
CR1 | 0.8 | 1.32 | NS | Receptor that plays a critical role in the capture and clearance of complement-opsonized pathogens. |
MARCO | −1.13 | −1.46 | 6.62 | Pattern recognition receptor (PRR) which binds bacteria. |
COLEC12 | −1.61 | NS | 3.37 | Scavenger receptor correlated to infiltration of suppressor immune cells. |
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Batista, L.F.S.; Sandoval Pacheco, C.M.; Flores, G.V.A.; Ferreira, F.M.; Gonçalves, A.N.A.; Sosa-Ochoa, W.H.; da Matta, V.L.R.; Gomes, C.M.C.; Zúniga, C.; Corbett, C.E.P.; et al. Molecular Insights into Cell-Mediated Immunity in Atypical Non-Ulcerated Cutaneous Leishmaniasis. Microorganisms 2025, 13, 413. https://doi.org/10.3390/microorganisms13020413
Batista LFS, Sandoval Pacheco CM, Flores GVA, Ferreira FM, Gonçalves ANA, Sosa-Ochoa WH, da Matta VLR, Gomes CMC, Zúniga C, Corbett CEP, et al. Molecular Insights into Cell-Mediated Immunity in Atypical Non-Ulcerated Cutaneous Leishmaniasis. Microorganisms. 2025; 13(2):413. https://doi.org/10.3390/microorganisms13020413
Chicago/Turabian StyleBatista, Luís Fábio S., Carmen M. Sandoval Pacheco, Gabriela V. Araujo Flores, Frederico M. Ferreira, André N. A. Gonçalves, Wilfredo H. Sosa-Ochoa, Vânia L. R. da Matta, Claudia M. C. Gomes, Concepción Zúniga, Carlos E. P. Corbett, and et al. 2025. "Molecular Insights into Cell-Mediated Immunity in Atypical Non-Ulcerated Cutaneous Leishmaniasis" Microorganisms 13, no. 2: 413. https://doi.org/10.3390/microorganisms13020413
APA StyleBatista, L. F. S., Sandoval Pacheco, C. M., Flores, G. V. A., Ferreira, F. M., Gonçalves, A. N. A., Sosa-Ochoa, W. H., da Matta, V. L. R., Gomes, C. M. C., Zúniga, C., Corbett, C. E. P., Jeffares, D. C., Nakaya, H. I., Silveira, F. T., & Laurenti, M. D. (2025). Molecular Insights into Cell-Mediated Immunity in Atypical Non-Ulcerated Cutaneous Leishmaniasis. Microorganisms, 13(2), 413. https://doi.org/10.3390/microorganisms13020413