Leishmania and HIV-1 interaction : immunopathogenic mechanisms
Author: Wolday, Dawit
Date: 2000-01-17
Location: Föreläsningssalen vid Mikrobiologiskt och Tumörbiologiskt Centrum (MTC), Theorells väg 7
Time: 9.00
Department: Mikrobiologiskt och Tumörbiologiskt Centrum (MTC) / Microbiology and Tumor Biology Center (MTC)
Abstract
Both Leishmania and HIV can infect and multiply in macrophages, and both
can dysregulate the T-helper (Th) immune system. This thesis was,
therefore, undertaken to unravel some of the underlying immunopathogenic
mechanisms of the interaction of the two pathogens.
Clinical findings at presentation in some of our visceral leishmaniasis
(VL)-HIV co-infected patients were atypical (i.e. absence of
organomegaly) with high parasite load, severe immunosuppression (low
CD4/CD8 ratio) and frequent relapse following successful initial
response. Heat-inactivated (HI)-HIV-1 inhibited Leishmania-induced cell
proliferation, but not IL-6 and TNF-[alpha] secretion, suggesting that
the parasite can activate HIV. In addition, both HI and live HIV led to
the uncontrolled growth of Leishmania in monocytes.
Stimulation of CD8-depleted peripheral blood mononuclear cells (PBMCs)
from asymptomatic HIV-1 infected persons with Leishmania or
lipophosphoglycan (LPG), a major membrane constituent of Leishmania,
resulted in HIV-1 replication, cellular immune activation CD4+T cell
apoptosis. Interestingly, the immunomodulatory compound thalidomide
inhibited Leishmania antigen-induced secretion of TNF-[alpha] and virus
replication, with no effect on IL-2 or IL-6 production, cellular
activation and apoptosis. They suggest that TNF-[alpha] secretion is
pivotal in the process of induction of HIV replication. Thalidomide may
be of potential use to reduce HIV disease progression in VL co-infected
patients. The in vitro findings were supported by the observations we
made in vivo; persistence of parasite and hence active VL in patients who
failed antileishmanial chemotherapy was associated with high HIV load
than in those who had good response to therapy. Moreover, proliferative
responses to PHA or Leishmania were lower in VL and/or HIV-infected
persons compared to healthy controls. PBMC from healthy donors produced
high levels of Th1 cytokine (IFN-[gamma]), Th1-inducing cyokines (IL-12 &
IL-18), and low Th2 cytokines (IL-4 & IL-10); HI-HIV abrogated the
production of IFN-[gamma] induced by Leishmania and augmented IL-4 and
IL- 10. In contrast, VL and/or HIV-infected produced low levels of Th I
or Th I -inducing cyokines, but high levels of IL-10. data suggest that
the inhibitory effect of HIV and VL on the proliferative and IFN-[gamma]
production was not only due to IL- 10, but also that the defect induced
by HIV and VL probably operate at the level of regulation of
IFN-[gamma]-inducing factors.
List of papers:
I. Berhe N, Hailu A, Wolday D, Negesse Y, Cenini P, Frommel D (1995). "Ethiopian visceral leishmaniasis patients co-infected with human immunodeficiency virus" Trans R Soc Trop Med Hyg 89(2): 205-207
Pubmed
II. Wolday D, Akuffo H, Britton S, Hathaway A, Sander B (1994). "HIV-1 inhibits Leishmania-induced cell proliferation but not production of interleukin-6 and tumour necrosis factor alpha" Scand J Immunol 39(4): 380-386
Pubmed
III. Wolday D, Akuffo H, Fessahaye G, Valantine A, Britton S. (1998). "Live and killed human immunodeficiency virus type-1 increases the intracellular growth of Leishmania donovani in monocyte-derived cells" Scand J Infect Dis 30(1): 29-34
Pubmed
IV. Wolday D, Akuffo H, Demissie A, Britton S (1999). "Role of Leishmania donovani and its lipophosphoglycan in CD4+ T-cell activation-induced human immunodeficiency virus replication" Infect Immun 67(10): 5258-5264
Pubmed
V. Berhe N, Wolday D, Hailu A, Abraham Y, Ali A, Gebre-Michael T, Desjeux P, Sönnerborg A, Akuffo H, Britton S (1999). "HIV viral load and response to antileishmanial chemotherapy in co-infected patients." AIDS 13(14): 1921-1925
Pubmed
VI. Wolday D, Berhe N, Britton S, Akuffo H (1970). "HIV-1 alters T-cell cytokines, IL-12, and IL-18 responses to the protozoan parsite Leishmania donovani" (Manuscript)
I. Berhe N, Hailu A, Wolday D, Negesse Y, Cenini P, Frommel D (1995). "Ethiopian visceral leishmaniasis patients co-infected with human immunodeficiency virus" Trans R Soc Trop Med Hyg 89(2): 205-207
Pubmed
II. Wolday D, Akuffo H, Britton S, Hathaway A, Sander B (1994). "HIV-1 inhibits Leishmania-induced cell proliferation but not production of interleukin-6 and tumour necrosis factor alpha" Scand J Immunol 39(4): 380-386
Pubmed
III. Wolday D, Akuffo H, Fessahaye G, Valantine A, Britton S. (1998). "Live and killed human immunodeficiency virus type-1 increases the intracellular growth of Leishmania donovani in monocyte-derived cells" Scand J Infect Dis 30(1): 29-34
Pubmed
IV. Wolday D, Akuffo H, Demissie A, Britton S (1999). "Role of Leishmania donovani and its lipophosphoglycan in CD4+ T-cell activation-induced human immunodeficiency virus replication" Infect Immun 67(10): 5258-5264
Pubmed
V. Berhe N, Wolday D, Hailu A, Abraham Y, Ali A, Gebre-Michael T, Desjeux P, Sönnerborg A, Akuffo H, Britton S (1999). "HIV viral load and response to antileishmanial chemotherapy in co-infected patients." AIDS 13(14): 1921-1925
Pubmed
VI. Wolday D, Berhe N, Britton S, Akuffo H (1970). "HIV-1 alters T-cell cytokines, IL-12, and IL-18 responses to the protozoan parsite Leishmania donovani" (Manuscript)
Issue date: 1999-12-27
Publication year: 1999
ISBN: 91-628-3814-8
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