Increased Leishmania Replication in HIV-1--Infected Macrophages Is Mediated by Tat Protein through Cyclooxygenase-2 Expression and Prostaglandin E2 Synthesis

Barreto-de-Souza, Victor; Pacheco, Graziela J.; Silva, Adriana R.; Castro-Faria-Neto, Hugo C.; Bozza, Patrícia T.; Saraiva, Elvira M.; Chequer Bou-Habib, Dumith
September 2006
Journal of Infectious Diseases;9/15/2006, Vol. 194 Issue 6, p846
Academic Journal
Protozoan parasites of the genus Leishmania frequently occur as opportunistic pathogens in human immunodeficiency virus type 1 (HIV-1)-infected individuals, but the mechanisms underlying protozoan growth in this context are poorly understood. Here, we demonstrate that the HIV-1 Tat protein drives Leishmania replication in primary human macrophages. We found that Leishmania growth doubled in HIV-1-infected macrophages and that anti-Tat antibodies reduced the exacerbated protozoan replication by 70%. Recombinant Tat increased Leishmania replication and overrode the leishmanicidal effect induced by interferon-γ, allowing Leishmania replication even in the presence of this cytokine. Tat induced cyclooxygenase (COX)-2 expression and prostaglandin E2 (PGE2) synthesis, and a COX-2 inhibitor abolished the Tat-mediated augmentation of Leishmania replication. Moreover, PGE2 increased Leishmania growth, which was abrogated by anti-transforming growth factor (TGF)-β1 monoclonal antibodies. Neutralization of TGF-β1 reduced parasite growth in Leishmania-infected macrophages exposed to Tat by 50%. Our findings suggest that Tat generates a milieu permissive to Leishmania growth in individuals infected with HIV-1.


Related Articles

  • Leishmania infantum Promastigotes Reduce Entry of HIV-1 into Macrophages through a Lipophosphoglycan-Mediated Disruption of Lipid Rafts. Garg, Ravendra; Lodge, Robert; Descoteaux, Albert; Tremblay, Michel J. // Journal of Infectious Diseases;6/15/2008, Vol. 197 Issue 12, p1701 

    Visceral leishmaniasis is now recognized as an opportunistic disease in patients infected with human immunodeficiency virus type 1 (HIV-1). We report here that Leishmania infantum promastigotes enhance HIV-1 replication in monocyte-derived macrophages (MDMs) at late time points in the virus...

  • Haemoculture as a tool for diagnosing visceral leishmaniasis in HIV-negative and HIV-positive... Dereure, J.; Pratlong, F.; Reynes, J.; Basset, D.; Bastien, P.; Dedet, J.-P. // Bulletin of the World Health Organization;1998, Vol. 76 Issue 2, p203 

    Presents information on the examination of 65 adults infected with human immunodeficiency virus (HIV), to test for leishmania. Details on the bone marrow and peripheral venous blood samples taken from these patients; Methodology used to gather the information; Results of the examination process.

  • INFLUENCE OF PROSTAGLANDINS E1, E2, AND ARACHIDONATE ON MELANOSOMES IN MELANOCYTES AND KERATINOCYTES OF ANAGEN HAIR BULBS IN VITRO. Sauk Jr., John J.; White, James G.; Witkop Jr., Carl J. // Journal of Investigative Dermatology;May75, Vol. 64 Issue 5, p332 

    Anagen hair bulbs were collected and maintained in organ culture for periods up to 24 hr. Prostaglandin E1, E2, and arachidonate were introduced to the cultures and stimulated a series of cellular events characterized by peripheral orientation of microfilaments in the dendritic processes of...

  • Evolutionary genetics and molecular diagnosis of Leishmania species. Bañuls, Anne-Laure; Hide, Mallorie; Tibayrenc, Michel // Transactions of the Royal Society of Tropical Medicine & Hygiene;Apr2004 Suppplement 1, Vol. 96, pS9 

    An extensive study has been performed on various natural populations of Leishmania from the ‘Old’ and ‘New Worlds’ using multilocus enzyme electrophoresis and random amplification of polymorphic deoxyribonucleic acid. The data are interpreted in evolutionary genetic...

  • Characteristics of Leishmania spp. isolated from a mixed focus of cutaneous and visceral Leishmaniasis in Himachal Pradesh (India). Sharma, Nand Lal; Sood, Anuradha; Arora, Sunil K.; Kanga, Anil; Mahajan, Vikram K.; Negi, Ajit K.; Sharma, Ashok K. // Internet Journal of Third World Medicine;2009, Vol. 7 Issue 2, p8 

    Background: A mixed endemic focus of cutaneous and visceral leishmaniasis has emerged along the Sutluj river valley of Himachal Pradesh (India). Methods: The laboratory work up of 218 new consecutive cases of localized cutaneous leishmaniasis (LCL) and 14 patients of visceral leishmaniasis (VL)...

  • A simple device to maintain in vitro cultures of Leishmania in tropical countries. Ihalamulla, R.L.; Liyanage, C.P.G.; Karunaweera, N.D. // Transactions of the Royal Society of Tropical Medicine & Hygiene;May2004, Vol. 98 Issue 5, p315 

    A thermo-stable clay device to maintain in vitro Leishmania cultures in tropical countries within the optimal temperature range of 22 to 27 °C was developed. This being simple and economical could immensely benefit diagnosis and research on leishmaniasis in these countries.

  • Leishmania isoenzyme polymorphisms in Ecuador: Relationships with geographic distribution and clinical presentation. Calvopina, Manuel; Armijos, Rodrigo X; Marco, Jorge D; Uezato, Hiroshi; Kato, Hirotomo; Gomez, Eduardo A; Korenaga, Masataka; Barroso, Paola A; Mimori, Tatsuyuki; Cooper, Philip J; Nonaka, Shigeo; Hashiguchi, Yoshihisa // BMC Infectious Diseases;2006, Vol. 6 Issue 1, p1 

    Background: Determinants of the clinical presentation of the leishmaniases are poorly understood but Leishmania species and strain differences are important. To examine the relationship between clinical presentation, species and isoenzyme polymorphisms, 56 Leishmania isolates from distinct...

  • Anti-leishmania activity of semi-purified fraction of Jacaranda puberula leaves. L. Passero; A. Castro; T. Tomokane; M. Kato; T. Paulinetti; C. Corbett; M. Laurenti // Parasitology Research;Aug2007, Vol. 101 Issue 3, p677 

    Abstract  The crude methanolic extract from leaves of Jacaranda puberula showed activity against Leishmania (Leishmania) amazonensis. The extract presented active against promastigote forms with an inhibitory concentration 50% (IC50) value of 88.0 μg/ml, but only...

  • The induction of cyclooxygenase-2 in IL-1beta-treated endothelial cells is inhibited by prostaglandin E[sub 2] through cAMP. Akarasereenont, Pravit; Techatrisak, Kitirat; Chotewuttakorn, Sirikul; Thaworn, Athiwat // Mediators of Inflammation;Dec99, Vol. 8 Issue 6, p287 

    Prostaglandins (PGS) have numerous cardiovascular and inflammatory effects. Cyclooxygenase (COX), which exists as COX-1 and COX-2 isoforms, is the first enzyme in the pathway in which arachidonic acid is converted to PGs. Prostaglandin E[sub 2] (PGE[sub 2]) exerts a variety of biological...


Read the Article


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

Try another library?
Sign out of this library

Other Topics