Increased natural killer activity does not prevent progression of experimental Kala-azar

Sartori, Alexandrina; Kaneno, Ramon; Baruzzi, Nelson; Peraçoli, Maria Terezinha Serrão

doi:10.1590/s0036-46651999000400002

Cited by 5 publications

(4 citation statements)

References 23 publications

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“…Given that the presence of granulomatous inflammation has been associated with sub-clinical infection with L. donovani and that in the mouse model of VL, disease is less progressive than in man (Kaye et al, 2004), our data demonstrating the modulation of parasite burden by NK cells suggests that IL-10-producing NK cells might have a more dominant role at early stages of human VL, perhaps contributing to the immunoregulatory balance that governs the transition from sub-clinical infection to clinical disease. Nevertheless, NK cell numbers do increase during fatal experimental visceral leishmaniasis in the hamster, a model often regarded as better reflecting end stage human disease (Sartori et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Posttranscriptional Regulation of Il10 Gene Expression Allows Natural Killer Cells to Express Immunoregulatory Function

et al. 2008

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Natural killer (NK) cells play a well-recognized role in early pathogen containment and in shaping acquired cell-mediated immunity. However, indirect evidence in humans and experimental models has suggested that NK cells also play negative regulatory roles during chronic disease. To formally test this hypothesis, we employed a well-defined experimental model of visceral leishmaniasis. Our data demonstrated that NKp46(+)CD49b(+)CD3(-) NK cells were recruited to the spleen and into hepatic granulomas, where they inhibited host protective immunity in an interleukin-10 (IL-10)-dependent manner. Although IL-10 mRNA could be detected in activated NK cells 24 hr after infection, the inhibitory function of NK cells was only acquired later during infection, coincident with increased IL-10 mRNA stability and an enhanced capacity to secrete IL-10 protein. Our data support a growing body of literature that implicates NK cells as negative regulators of cell-mediated immunity and suggest that NK cells, like CD4(+) T helper 1 cells, may acquire immunoregulatory functions as a consequence of extensive activation.

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Section: Discussionmentioning

confidence: 99%

Posttranscriptional Regulation of Il10 Gene Expression Allows Natural Killer Cells to Express Immunoregulatory Function

et al. 2008

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“…The finding that the therapeutic effect of recombinant IL-12 in L. donovani -infected mice was prevented in anti-asialo-GM1-treated mice is likewise compatible with a beneficial role of NK cells (Murray and Hariprashad, 1995), but might also result from the activity of NKT cells (Amprey et al, 2004). Independent of a possible protective effect of NK cells in wild-type mice, additional studies in cytokine- or amphotericin B-treated nude mice (B- and T-cell-deficient) and euthymic bg/bg mice (defective NK cells) as well as in the hamster model of VL revealed that NK cells are neither sufficient nor essential to control L. donovani (Murray et al, 1995; Sartori et al, 1999; Murray, 2005). In addition, one study even demonstrated that activated, IL-10-expressing NK cells antagonized the control of L. donovani in the spleen and in the liver as shown by cell depletion and adoptive transfer experiments (Maroof et al, 2008) (Figure 1).…”

Section: Function Of Nk Cells In Mouse and Human Leishmaniasismentioning

confidence: 99%

Natural killer cells in experimental and human leishmaniasis

Bogdan

2012

Front. Cell. Inf. Microbio.

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Infections with parasites of the genus Leishmania lead to a rapid, but transient activation of natural killer (NK) cells. In mice activation of NK cells requires a toll-like-receptor 9-dependent stimulation of dendritic cells (DC) which is followed by the production of IL-12. Although NK cells appear to be non-essential for the ultimate control of cutaneous and visceral leishmaniasis (VL) and can exhibit immunosuppressive functions, they form an important source of interferon (IFN)-γ, which elicits antileishmanial activity in macrophages and helps to pave a protective T helper cell response. In contrast, the cytotoxic activity of NK cells is dispensable, because Leishmania-infected myeloid cells are largely resistant to NK-mediated lysis. In human cutaneous and VL, the functional importance of NK cells is suggested by reports that demonstrate (1) a direct activation or inhibition of NK cells by Leishmania promastigotes, (2) the suppression of NK cell numbers or activity during chronic, non-healing infections, and (3) the recovery of NK cell activity following treatment. This review aims to provide an integrated view on the migration, activation, inhibition, function, and therapeutic modulation of NK cells in experimental and human leishmaniasis.

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“…The collapse of the venous sinus architecture might be the response for the initial congestive and massively enlarged spleen typical of initial visceral leishmanioses. Sartori et al (1999) showed a significant increase in the spleen weight and spleen cell number (NK efector cells or natural killer cells). We should underline the idea that beyond the new reticular meshwork conditions, we cannot exclude other elements that may behave as a ''barrier'' condition, such as immunogical cells that can be so numerous and tightly packed that they physically impede the flow of free cells and blood through the spleen.…”

Section: Discussionmentioning

confidence: 99%

Leishmaniosis—A report about the microvascular and cellular architecture of the infected spleen inCanis familiaris

Alexandre‐Pires¹,

Pais²,

Correia³

et al. 2006

Microsc. Res. Tech.

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Leishmaniosis is an anthropozoonosis caused by an intracellular protozoan parasite that causes a wide spectrum of diseases in humans and dogs worldwide. In the Mediterranean basin, Portugal, Central and South America, and in the Middle East, visceral leishmaniosis is caused by Leishmania infantum. In these areas, dogs are believed to be the natural reservoirs of this parasite. In the case of visceral leishmaniosis, the spleen is one of the several hematopoietic and immunocompetent organs involved. Since this viscera is a blood filter, the authors investigated the expression of the morphological and microvascular environment and modifications of the spleen cell population related to immunological responses to this parasitic condition. The tools used to perform this study were scanning electronic microscopy of intact tissue and corrosion casts, transmission electronic microscopy, histology and immunohistochemistry. The results reveal three important modifications concerning the spleen's microvascular architecture when compared with its normal pattern, independently of the serological titer obtained with indirect immunofluorescence. (1) A marked scarcity of the sinusoidal system sheet that surrounds the central artery/arteriole of the white pulp; (2) A huge development of pulp venules and veins; (3) The presence of a surprising development of reticular fibers. The authors postulate that independent of the virulence of the parasite involved and the type of immunity prevalent in a particular host, the spleen develops blood dynamic conditions that permit reduction in the speed of blood flow so that cells involved in immunological processes can proliferate and differentiate, and also contributes to trapping lymphocytes within the area through the differentiation of characteristics that resemble those of HEV endothelial cells.

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Increased natural killer activity does not prevent progression of experimental Kala-azar

Cited by 5 publications

References 23 publications

Posttranscriptional Regulation of Il10 Gene Expression Allows Natural Killer Cells to Express Immunoregulatory Function

Posttranscriptional Regulation of Il10 Gene Expression Allows Natural Killer Cells to Express Immunoregulatory Function

Natural killer cells in experimental and human leishmaniasis

Leishmaniosis—A report about the microvascular and cellular architecture of the infected spleen inCanis familiaris

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