Immunological factors governing resistance and susceptibility of mice to Leishmania major infection (original) (raw)
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European Journal of Immunology, 1995
The most important immunopathological consequence of infection with Leishmania seen in murine and human hosts is the suppression of T cell-mediated immune responses to both mitogens and leishmanial antigens. It has been suggested that this suppression is mediated by macrophages, either by defective antigen processing and presentation or by the elaboration of suppressive mediators like prostaglandins. Optimum activation of T helper cells requires not only T cell receptor occupancy by the antigen-Ia complex, but also costimulatory signals provided by the antigen-presenting cells. We investigated the status of several costimulatory molecules on infected macrophages from both genetically susceptible BALB/c and resistant C57BL/6 mice. Our results demonstrate that upon parasitization, the macrophages become unable to deliver costimulatory signals to T helper cells, and that this effects is mediated by prostaglandins, as the inhibition of its synthesis by indomethacin recovered the defect. Upon infection with L. donovani, B7-1 expression was decreased, while ICAM-1 was marginally increased in BALB/c macrophages and there was no significant change in the expression of B7-1 and ICAM-1 in Leishmania-infected C57BL/6 macrophages. Expression of VCAM-1 did not change during infection. This selective alteration in the expression of costimulatory molecules on L. donovani-infected BALB/c macrophages was caused by the living parasite, as shown by the fact that killing of the parasites by stibogluconate led to no alteration in the levels of costimulatory molecules. We found that the change in B7-1 expression on the surface of infected macrophages resulted in the inhibition of delayed-type hypersensitivity-mediating functions of T helper cells from BALB/c mice. The results described in this study not only throw light on the possible mechanism of leishmanial pathogenesis, but also open up the possibility of immunotherapy of leishmaniasis by selective manipulation of costimulatory molecules.
Infection and immunity, 1986
Spleen cells from BALB/c mice infected with 2 X 10(7) L. major promastigotes and developing progressive disease produced significantly lower levels of interleukin-2 (IL-2) in response to concanavalin A stimulation than did spleen cells from uninfected mice. In contrast, spleen cells from sublethally irradiated and infected mice, which were able to contain lesion development, produced significantly higher levels of IL-2. The increase in IL-2 production closely paralleled lesion regression. Mice protectively immunized by four intravenous injections with lethally irradiated promastigotes also produced enhanced levels of IL-2, which were sustained after challenge infection. In contrast, spleen cells from BALB/c mice given four s.c. injections of irradiated promastigotes produced high levels of IL-2 before but not after infection. These mice eventually produced levels of IL-2 indistinguishable from those of unimmunized mice with progressive disease. There is thus an inverse relation betw...
Cytokine Gene Expression Alterations in Human Macrophages Infected by Leishmania major
Cell J. 2021; 22(4): 476-481., 2021
Objective: Leishmaniasis is caused by members of the Leishmania species and constitute a group of infective diseases that range from cutaneous lesions to lethal visceral forms. In infected persons, macrophages recognize and eliminate the parasites via phagocytosis. In order to change a hostile environment into an environment adequate for survival and reproduction, the engulfed Leishmania species needs to modulate the function of its host macrophage. The expression patterns of cytokine genes such as interleukin-12 (IL-12), tumour necrosis factor-alpha (TNF-α), IL-1, and interferon-gamma (IFNγ) represent the immune response. In this study, we employed an RNA-seq approach for human monocyte-derived macrophages infected with Leishmania major (L. major) to decipher cytokine gene expression alterations in host macrophages. Materials and Methods: In this descriptive study, human monocytes were isolated by magnetic activated cell sorting (MACS) and cultured in the presence of monocyte colony stimulating factor (M-CSF) to obtain the macrophages. Monocyte-derived macrophages were then co-cultured with metacyclic promastigotes of L. major for 4 hours. RNA isolation was performed using TRIzol reagent. RNA sequencing was performed using the Illumina sequencing platforms. Gene expression analysis was performed using a Bioconductor DESeq2 package. Results: Our data revealed significant changes in immune response gene expressions in macrophages infected with L. major, with an up-regulation of cytokines and mostly down-regulation of their receptors. Conclusion: The obtained data could shed more light on the biology of L. major and how the host cell responds to leishmaniasis.