Leishmania recombinant antigen modulates macrophage effector function facilitating early clearance of intracellular parasites

Ratna, Anuradha; Arora, Sunil K.
October 2016
Transactions of the Royal Society of Tropical Medicine & Hygiene;Oct2016, Vol. 110 Issue 10, p610
Academic Journal
Background: Immunmodulation combined with chemotherapy has emerged as an alternative to treat infections. The study evaluates immunomodulatory properties of a Leishmania recombinant protein (rA6) in activating macrophages and clearing intracellular parasites. Methods: The rA6 from a previously identified cDNA clone was analyzed for inducing the production of nitric oxide (NO) and reactive oxygen species (ROS) in macrophages, post and prior to infection with promastigotes by Griess method and flow cytometry. Phagocytosis and killing by treated macrophages was evaluated using Staphylococcus aureus as an index organism. Intracellular clearance of PKH67-labeled parasites from treated macrophages was assessed flowcytometrically. Combined effect of rA6 with miltefosine/AmBisome in reducing intracellular amastigotes was examined microscopically. Results: Treatment with rA6 post infection caused increased production of NO with increased number of macrophages producing NO and ROS coupled with enhanced phagocytic and killing capacity. Antigen stimulated macrophages expressed high level of iNOS and TNF-α mRNA. It synergized with miltefosine and AmBisome and facilitated early clearance of intracellular amastigotes at sub-optimal drug doses. Conclusion: The study demonstrates immunomodulatory potential of rA6 and presents first evidence on synergism between rA6 and anti-leishmanial drugs, thus placing it as a promising candidate for adjunct therapy.


Related Articles

  • Indeterminate Cell Histiocytosis: Report of a Case. Ghanadan, Alireza; Kamyab, Kambiz; Ramezani, Mazaher; Goodarzi, Azadeh; Daneshpazhooh, Maryam; Balighi, Kamran; Ansari, Mahsa; Mirfallah Nassiri, Seyed Farzad; Daklan, Soroush // Acta Medica Iranica;2014, Vol. 52 Issue 10, p789 

    Indeterminate cell histiocytosis is a very rare disorder of histiocytes proliferation. It has both Langerhans and non-Langerhans cell histiocytosis immunophenotypic features. We described a 45-year-old man with a 2 years history of multiple yellow-brown papules and a few red nodules on his trunk...

  • CARDIAC INVOLVEMENT IN ERDHEIM-CHESTER DISEASE: A CASE REPORT. Júnior, Fernando Pivatto; Piardi, Diogo Silva; Torres, Felipe Soares // Clinical & Biomedical Research;2014, Vol. 34 Issue 4, p406 

    Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis of unknown etiology characterized by proliferation of lipid-containing foamy histiocytes affecting bones and potentially every organ. There is a wide clinical spectrum of the disease, ranging from asymptomatic bone or...

  • Treatment failure by canakinumab in a patient with progressive multisystemic Erdheim-Chester disease refractory to anakinra: successful use of vemurafenib. Schirmer, Jan H.; Thorns, Christoph; Moosig, Frank; Holle, Julia U. // Rheumatology;Oct2015, Vol. 54 Issue 10, p1932 

    A letter to the editor is presented in response to a case report by T-A Tran et al which describes the efficacy of canakinumab, a mAb directed against human IL-1B in Erdheim-Chester disease (ECD).

  • Fludarabine in the treatment of an active phase of a familial haemophagocytic lymphohistiocytosis. Schneider, P.; Greene, V.; Kanold, J.; Vannier, J. -P. // Archives of Disease in Childhood;Apr2001, Vol. 84 Issue 4, p373 

    Presents a letter to the editor about fludarabine in the treatment of an active phase of a familial haemophagocytic lymphohistiocytosis.

  • Treatment of Erdheim–Chester disease with canakinumab. Tran, Tu-Anh; Pariente, Danièle; Guitton, Corinne; Delwail, Adriana; Barat-Houari, Mouna; Meinzer, Ulrich // Rheumatology;Dec2014, Vol. 53 Issue 12, p2312 

    A letter to the editor is presented in response to the article "Treatment of Erdheim-Chester disease with canakinumab" in the September 17, 2014 issue.

  • Multicentric reticulohistiocytosis: case report with response to infliximab and review of treatment options. Macía-Villa, Cristina; Zea-Mendoza, Antonio // Clinical Rheumatology;Feb2016, Vol. 35 Issue 2, p527 

    Multicentric reticulohistiocytosis (MRH) is a rare systemic and devastating disease with main involvement of skin and joints, frequently related with malignancies. Macrophages and TNFα are the main targets of multiple treatment options with variable results. Although MRH has the tendency of...

  • Leishmania (Viannia) braziliensis Inositol Phosphorylceramide: Distinctive Sphingoid Base Composition. De Castro Levatti, Erica V.; Toledo, Marcos S.; Costa, Renata Watanabe; Bahia, Diana; Mortara, Renato A.; Takahashi, Helio K.; Straus, Anita H. // Frontiers in Microbiology;8/4/2017, p1 

    Inositol phosphorylceramide (IPC), the major sphingolipid in the genus Leishmania but not found in mammals, is considered a potentially useful target for chemotherapy against leishmaniasis. Leishmania (Viannia) braziliensis is endemic in Latin America and causes American tegumentary...

  • Simultaneous transcriptional profiling of Leishmania major and its murine macrophage host cell reveals insights into host-pathogen interactions. Dillon, Laura A. L.; Suresh, Rahul; Orah, Kwame; Bravo, Hector Corrada; Mosser, David M.; El-Sayed, Najib M. // BMC Genomics;12/29/2015, Vol. 16, p1 

    Background: Parasites of the genus Leishmania are the causative agents of leishmaniasis, a group of diseases that range in manifestations from skin lesions to fatal visceral disease. The life cycle of Leishmania parasites is split between its insect vector and its mammalian host, where it...

  • Benign cephalic histiocytosis. Kambil, Srinath M.; Chauhan, Ravikant; Bhat, Ramesh M.; Dandekeri, Sukumar // Indian Journal of Paediatric Dermatology;Oct-Dec2015, Vol. 16 Issue 4, p274 

    The article discusses the medical case of a newborn infant diagnosed with benign cephalic histiocytosis, a type of nonlangerhan cell histiocytosis, which was found on the cheeks, ears, and chin region of the body.


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics