TY - JOUR
T1 - The Immunology of a Healing Response in Cutaneous Leishmaniasis Treated with Localized Heat or Systemic Antimonial Therapy
AU - Lakhal-Naouar, Ines
AU - Slike, Bonnie M.
AU - Aronson, Naomi E.
AU - Marovich, Mary A.
N1 - Funding Information:
The authors thank the Thermomed study participants, research nurses and physicians; these data would not be available without their participation. The laboratory assistance of Tina Libby-Tong, Maureen Stefaniak, and Doris Thelian was invaluable. We appreciate the critical reviews of Dr. Andréa Teixeira de Carvalho and the assistance of Dr. Cara Olsen with the statistical analysis. We acknowledge the support of the U.S. Army Medical Materiel Development Activity as study sponsor.
Funding Information:
This work was supported by Department of Defense Global War on Terrorism funds and by a cooperative agreement [W81XWH-07-2-0067] between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. and the U.S. Department of Defense (DOD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Funding Information:
Funding: This work was supported by Department of Defense Global War on Terrorism funds and by a cooperative agreement [W81XWH-07-2-0067] between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. and the U.S. Department of Defense (DOD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2015, Public Library of Science, All Rights Reserved.
PY - 2015/10/20
Y1 - 2015/10/20
N2 - 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. Conclusion: 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.
AB - 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. Conclusion: 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.
UR - http://www.scopus.com/inward/record.url?scp=84959364028&partnerID=8YFLogxK
U2 - 10.1371/journal.pntd.0004178
DO - 10.1371/journal.pntd.0004178
M3 - Article
C2 - 26485398
AN - SCOPUS:84959364028
SN - 1935-2727
VL - 9
JO - PLoS Neglected Tropical Diseases
JF - PLoS Neglected Tropical Diseases
IS - 10
M1 - e0004178
ER -