The Immunology of a Healing Response in Cutaneous Leishmaniasis Treated with Localized Heat or Systemic Antimonial Therapy.
BACKGROUND
The effectiveness of systemic antimonial (sodium stibogluconate, Pentostam, SSG) treatment versus local heat therapy (Thermomed) for cutaneous leishmaniasis was studied previously and showed similar healing rates. We hypothesized that different curative immune responses might develop with systemic and local treatment modalities.


METHODS
We studied the peripheral blood immune cells in a cohort of 54 cutaneous Leishmania major subjects treated with SSG or TM. Multiparameter flow cytometry, lymphoproliferative assays and cytokine production were analyzed in order to investigate the differences in the immune responses of subjects before, on and after treatment.


RESULTS
Healing cutaneous leishmaniasis lead to a significant decline in circulating T cells and NKT-like cells, accompanied by an expansion in NK cells, regardless of treatment modality. Functional changes involved decreased antigen specific CD4+ T cell proliferation (hyporesponsiveness) seen with CD8+ T cell depletion. Moreover, the healing (or healed) state was characterized by fewer circulating regulatory T cells, reduced IFN-γ production and an overall contraction in polyfunctional CD4+ T cells.


CONCLUSIONS
Healing from cutaneous Leishmaniasis is a dynamic process that alters circulating lymphocyte populations and subsets of T, NK and NKT-like cells. Immunology of healing, through local or systemic treatments, culminated in similar changes in frequency, quality, and antigen specific responsiveness with immunomodulation possibly via a CD8+ T cell dependent mechanism. Understanding the evolving immunologic changes during healing of human leishmaniasis informs protective immune mechanisms.
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States of America.
Ines
I
Lakhal-Naouar
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States of America; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
Bonnie M
BM
Slike
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America; Walter Reed National Military Medical Center, Bethesda, Maryland, United States of America.
Naomi E
NE
Aronson
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America; Walter Reed National Military Medical Center, Bethesda, Maryland, United States of America.
Mary A
MA
Marovich
D000293:Adolescent; D000328:Adult; D000965:Antimony / Q000008:administration & dosage*; D049109:Cell Proliferation; D015331:Cohort Studies; D004358:Drug Therapy / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology / Q000628:therapy*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D007371:Interferon-gamma; D000965:Antimony