Molecular Insights into Cell-Mediated Immunity in Atypical Non-Ulcerated Cutaneous Leishmaniasis

被引:0
作者
Batista, Luis Fabio S. [1 ]
Pacheco, Carmen M. Sandoval [1 ]
Flores, Gabriela V. Araujo [1 ]
Ferreira, Frederico M. [1 ]
Goncalves, Andre N. A. [2 ]
Sosa-Ochoa, Wilfredo H. [3 ]
da Matta, Vania L. R. [1 ]
Gomes, Claudia M. C. [1 ]
Zuniga, Concepcion [4 ]
Corbett, Carlos E. P. [1 ]
Jeffares, Daniel C. [5 ]
Nakaya, Helder I. [2 ,6 ]
Silveira, Fernando T. [7 ]
Laurenti, Marcia D. [1 ]
机构
[1] Univ Sao Paulo, Dept Pathol, Med Sch, BR-01246903 Sao Paulo, Brazil
[2] Univ Sao Paulo, Dept Clin & Toxicol Anal, BR-05508000 Sao Paulo, Brazil
[3] Natl Autonomous Univ Honduras, Microbiol Res Inst, Tegucigalpa 11101, Honduras
[4] Natl Autonomous Univ Honduras, Dept Hlth Surveillance, Tegucigalpa 05005, Honduras
[5] Univ York, York Biomed Res Inst, Dept Biol, York YO31 5DD, England
[6] Hosp Israelita Albert Einstein, Sao Paulo, Brazil
[7] Evandro Chagas Inst, BR-66093020 Belem, Brazil
基金
巴西圣保罗研究基金会;
关键词
atypical non-ulcerated cutaneous leishmaniasis; visceral leishmaniasis; <italic>L.</italic> (<italic>L.</italic>) <italic>infantum chagasi</italic>; transcriptome; cell-mediated immune response; HUMAN DENDRITIC CELLS; T-CELLS; EXPRESSION; CHAGASI; PATHWAY; INHIBITION; ACTIVATION; RESPONSES; INFANTUM; DISTINCT;
D O I
10.3390/microorganisms13020413
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Leishmania (Leishmania) infantum chagasi infections range from asymptomatic (AS) to severe visceral leishmaniasis (VL). One of the manifestations is an atypical non-ulcerated cutaneous leishmaniasis (NUCL), which occurs in some locations of Central America with few cases of VL. We conducted a transcriptomic analysis of cell-mediated immunity (CMI) on blood samples from NUCL, AS, VL patients from Amapala, Honduras, and healthy controls. RNA-seq revealed a similar perturbation of gene expression in NUCL and AS. Eight gene signatures of CMI were found in NUCL involved in CD8+ T lymphocyte infiltration, reactive oxygen species generation, PD-1 receptor ligand, inflammasome assembly, chemotaxis, complement receptor and suppressor immune cell infiltration. NUCL was distinguished from VL by its up-regulation of differently expressed genes (DEGs) related to T lymphocyte exhaustion, adhesion and transmigration of leukocytes, and down-regulation of oxidative stress genes. In contrast, VL exhibited up-regulated DEGs involved in antigen cross-presentation, and similar to VL from Brazil, down-regulated DEGs involved in innate immunity. Corroborating the transcriptome findings, both the Leishmanin skin test, and the immunopathology of NUCL skin lesion defined NUCL as a proinflammatory condition, intermediate between the AS and VL clinical outcomes. That condition may be the underlying element for the benign nature of the NUCL.
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页数:20
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  • [1] Ponce C., Ponce E., Morrison A., Cruz A., Kreutzer R., McMahon-Pratt D., Neva F., Leishmania donovani chagasi: New clinical variant of cutaneous leishmaniasis in Honduras, Lancet, 337, pp. 67-70, (1991)
  • [2] Noyes H., Chance M., Ponce C., Ponce E., Maingon R., Leishmania chagasi: Genotypically similar parasites from Honduras cause both visceral and cutaneous leishmaniasis in humans, Exp. Parasitol, 85, pp. 264-273, (1997)
  • [3] Sandoval Pacheco C.M., Araujo Flores G.V., Ferreira A.F., da Matta V.L.R., de Castro Gomes C.M., Sosa-Ochoa W.H., Zuniga C., Silveira F.T., Corbett C.E.P., Laurenti M.D., Role of antigen-presenting cells in non-ulcerated skin lesions caused by Leishmania (Leishmania) infantum chagasi, Parasite Immunol, 45, (2023)
  • [4] Pearson R.D., Sousa A.D.Q., Clinical Spectrum of Leishmaniasis, Clin. Infect. Dis, 22, pp. 1-13, (1996)
  • [5] da Matta V.L.R., Goncalves A.N., Gomes C.M.C., Chouman I.H., Ferreira F.M., Campos M.B., Lima L.V., Vasconcelos Dos Santos T., Ramos P.K., Furtado R.R., Et al., Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by Leishmania (L.) chagasi in Amazonian Brazil, Microorganisms, 11, (2023)
  • [6] Sandoval Pacheco C.M., Araujo Flores G.V., Favero Ferreira A., Sosa Ochoa W., Ribeiro da Matta V.L., Zuniga Valeriano C., Pereira Corbett C.E., Dalastra Laurenti M., Histopathological features of skin lesions in patients affected by non-ulcerated or atypical cutaneous leishmaniasis in Honduras, Central America, Int. J. Exp. Pathol, 99, pp. 249-257, (2018)
  • [7] Yadav P., Azam M., Ramesh V., Singh R., Unusual Observations in Leishmaniasis—An Overview, Pathogens, 12, (2023)
  • [8] Morgan D.J., Guimaraes L.H., Machado P.R., D'Oliveira A., Almeida R.P., Lago E.L., Faria D.R., Tafuri W.L., Dutra W.O., Carvalho E.M., Cutaneous leishmaniasis during pregnancy: Exuberant lesions and potential fetal complications, Clin. Infect. Dis, 45, pp. 478-482, (2007)
  • [9] Lago T., Carvalho L.P., Nascimento M., Guimaraes L.H., Lago J., Castellucci L., Carvalho A.M., Lago A., Carvalho E.M., Influence of Obesity on Clinical Manifestations and Response to Therapy in Cutaneous Leishmaniasis Caused by Leishmania braziliensis, Clin. Infect. Dis, 73, pp. 1020-1026, (2021)
  • [10] Lago A.S., Lima F.R., Carvalho A.M., Sampaio C., Lago N., Guimaraes L.H., Lago J., Machado P.R.L., Carvalho L.P., Arruda S., Et al., Diabetes Modifies the Clinic Presentation of Cutaneous Leishmaniasis, Open Forum Infect. Dis, 7, (2020)