Host-Directed Therapies for Cutaneous Leishmaniasis

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Apr 12

PMID 33841444

Citations 12

Authors

Fernanda O Novais

Camila Farias Amorim

Phillip Scott

Affiliations

Soon will be listed here.

Abstract

Cutaneous leishmaniasis exhibits a wide spectrum of clinical presentations from self-resolving infections to severe chronic disease. Anti-parasitic drugs are often ineffective in the most severe forms of the disease, and in some cases the magnitude of the disease can result from an uncontrolled inflammatory response rather than unrestrained parasite replication. In these patients, host-directed therapies offer a novel approach to improve clinical outcome. Importantly, there are many anti-inflammatory drugs with known safety and efficacy profiles that are currently used for other inflammatory diseases and are readily available to be used for leishmaniasis. However, since leishmaniasis consists of a wide range of clinical entities, mediated by a diverse group of leishmanial species, host-directed therapies will need to be tailored for specific types of leishmaniasis. There is now substantial evidence that host-directed therapies are likely to be beneficial beyond autoimmune diseases and cancer and thus should be an important component in the armamentarium to modulate the severity of cutaneous leishmaniasis.

Citing Articles

Lack of Hypoxia Inducible Factor-1α Influences on Macrophages Ability to Deal with In Vitro and Affects Pathology In Vivo.

Sanches R, Vaz L, Marinho F, Guimaraes E, Carvalho E, Carvalho L JID Innov. 2025; 5(3):100347.

PMID: 39990593 PMC: 11847524. DOI: 10.1016/j.xjidi.2025.100347.

Distinct neutrophil effector functions in response to different isolates of Leishmania aethiopica.

Adem E, Cruz Cervera E, Yizengaw E, Takele Y, Shorter S, Cotton J Parasit Vectors. 2024; 17(1):461.

PMID: 39529155 PMC: 11555981. DOI: 10.1186/s13071-024-06489-x.

Investigation of parasite genetic variation and systemic immune responses in patients presenting with different clinical presentations of cutaneous leishmaniasis caused by Leishmania aethiopica.

Yizengaw E, Takele Y, Franssen S, Gashaw B, Yimer M, Adem E Infect Dis Poverty. 2024; 13(1):76.

PMID: 39415297 PMC: 11484111. DOI: 10.1186/s40249-024-01244-x.

Diagnostic challenges in cutaneous leishmaniasis due to atypical : pathologists' insights from re-emergence zones.

Ekemen S, Nalcaci M, Toz S, Sanjoba C, Demirkesen C, Cetin E Front Med (Lausanne). 2024; 11:1453211.

PMID: 39328317 PMC: 11425964. DOI: 10.3389/fmed.2024.1453211.

Targeting and activation of macrophages in leishmaniasis. A focus on iron oxide nanoparticles.

Palomino-Cano C, Moreno E, Irache J, Espuelas S Front Immunol. 2024; 15:1437430.

PMID: 39211053 PMC: 11357945. DOI: 10.3389/fimmu.2024.1437430.

References

Sacks D, Noben-Trauth N . The immunology of susceptibility and resistance to Leishmania major in mice. Nat Rev Immunol. 2002; 2(11):845-58. DOI: 10.1038/nri933. View

Gautam S, Kumar R, Maurya R, Nylen S, Ansari N, Rai M . IL-10 neutralization promotes parasite clearance in splenic aspirate cells from patients with visceral leishmaniasis. J Infect Dis. 2011; 204(7):1134-7. PMC: 3164427. DOI: 10.1093/infdis/jir461. View

Nabors G, Afonso L, Farrell J, Scott P . Switch from a type 2 to a type 1 T helper cell response and cure of established Leishmania major infection in mice is induced by combined therapy with interleukin 12 and Pentostam. Proc Natl Acad Sci U S A. 1995; 92(8):3142-6. PMC: 42121. DOI: 10.1073/pnas.92.8.3142. View

Da Silva Santos C, Boaventura V, Cardoso C, Tavares N, Lordelo M, Noronha A . CD8(+) granzyme B(+)-mediated tissue injury vs. CD4(+)IFNγ(+)-mediated parasite killing in human cutaneous leishmaniasis. J Invest Dermatol. 2013; 133(6):1533-40. PMC: 3667352. DOI: 10.1038/jid.2013.4. View

Martins F, Sofiya L, Sykiotis G, Lamine F, Maillard M, Fraga M . Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance. Nat Rev Clin Oncol. 2019; 16(9):563-580. DOI: 10.1038/s41571-019-0218-0. View

Burke K, Grebinoski S, Sharpe A, Vignali D . Understanding adverse events of immunotherapy: A mechanistic perspective. J Exp Med. 2021; 218(1). PMC: 7754677. DOI: 10.1084/jem.20192179. View

Sansonetti P, Lagrange P . The immunology of leprosy: speculations on the leprosy spectrum. Rev Infect Dis. 1981; 3(3):422-69. DOI: 10.1093/clinids/3.3.422. View

da Fonseca-Martins A, Ramos T, Pratti J, Firmino-Cruz L, Gomes D, Soong L . Immunotherapy using anti-PD-1 and anti-PD-L1 in Leishmania amazonensis-infected BALB/c mice reduce parasite load. Sci Rep. 2020; 9(1):20275. PMC: 6937231. DOI: 10.1038/s41598-019-56336-8. View

Unger A, ONeal S, Machado P, Guimaraes L, Morgan D, Schriefer A . Association of treatment of American cutaneous leishmaniasis prior to ulcer development with high rate of failure in northeastern Brazil. Am J Trop Med Hyg. 2009; 80(4):574-9. PMC: 3557504. View

10.

Gonzalez-Tafoya E, Diupotex M, Zamora-Chimal J, Salaiza-Suazo N, Ruiz-Remigio A, Becker I . TNF contributes to T-cell exhaustion in chronic L. mexicana infections of mice through PD-L1 up-regulation. Cell Immunol. 2020; 358:104196. DOI: 10.1016/j.cellimm.2020.104196. View

11.

Crosby E, Clark M, Novais F, Wherry E, Scott P . Lymphocytic Choriomeningitis Virus Expands a Population of NKG2D+CD8+ T Cells That Exacerbates Disease in Mice Coinfected with Leishmania major. J Immunol. 2015; 195(7):3301-10. PMC: 4575880. DOI: 10.4049/jimmunol.1500855. View

12.

Brito G, Dourado M, Guimaraes L, Meireles E, Schriefer A, de Carvalho E . Oral Pentoxifylline Associated with Pentavalent Antimony: A Randomized Trial for Cutaneous Leishmaniasis. Am J Trop Med Hyg. 2017; 96(5):1155-1159. PMC: 5417210. DOI: 10.4269/ajtmh.16-0435. View

13.

Almeida R, Brito J, Machado P, de Jesus A, Schriefer A, Guimaraes L . Successful treatment of refractory cutaneous leishmaniasis with GM-CSF and antimonials. Am J Trop Med Hyg. 2005; 73(1):79-81. View

14.

Kolde G, Luger T, Sorg C, Sunderkotter C . Successful treatment of cutaneous leishmaniasis using systemic interferon-gamma. Dermatology. 1996; 192(1):56-60. DOI: 10.1159/000246316. View

15.

Christensen S, Dillon L, Carvalho L, Passos S, Novais F, Hughitt V . Meta-transcriptome Profiling of the Human-Leishmania braziliensis Cutaneous Lesion. PLoS Negl Trop Dis. 2016; 10(9):e0004992. PMC: 5025153. DOI: 10.1371/journal.pntd.0004992. View

16.

FALCOFF E, Taranto N, Remondegui C, Dedet J, Canini L, Ripoll C . Clinical healing of antimony-resistant cutaneous or mucocutaneous leishmaniasis following the combined administration of interferon-gamma and pentavalent antimonial compounds. Trans R Soc Trop Med Hyg. 1994; 88(1):95-7. DOI: 10.1016/0035-9203(94)90518-5. View

17.

Afonso L, Scott P . Immune responses associated with susceptibility of C57BL/10 mice to Leishmania amazonensis. Infect Immun. 1993; 61(7):2952-9. PMC: 280944. DOI: 10.1128/iai.61.7.2952-2959.1993. View

18.

Novais F, Carvalho L, Passos S, Roos D, Carvalho E, Scott P . Genomic profiling of human Leishmania braziliensis lesions identifies transcriptional modules associated with cutaneous immunopathology. J Invest Dermatol. 2014; 135(1):94-101. PMC: 4268311. DOI: 10.1038/jid.2014.305. View

19.

Scharton-Kersten T, Afonso L, Wysocka M, Trinchieri G, Scott P . IL-12 is required for natural killer cell activation and subsequent T helper 1 cell development in experimental leishmaniasis. J Immunol. 1995; 154(10):5320-30. View

20.

Kautz-Neu K, Kostka S, Dinges S, Iwakura Y, Udey M, von Stebut E . A role for leukocyte-derived IL-1RA in DC homeostasis revealed by increased susceptibility of IL-1RA-deficient mice to cutaneous leishmaniasis. J Invest Dermatol. 2011; 131(8):1650-9. PMC: 6999703. DOI: 10.1038/jid.2011.99. View