The role of polymorphonuclear leukocytes in the resistance to cutaneous Leishmaniasis

Lima, Glória M.A.C; Vallochi, Adriana Lima; Silva, Ulisses R; Bevilacqua, Estela; Kiffer, Maı́sa M.F; Abrahamsohn, Ises A.

doi:10.1016/s0165-2478(98)00099-6

Cited by 73 publications

(83 citation statements)

References 28 publications

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“…We and others [18,33,34] have demonstrated that neutrophils play a primordial role in the containment of this parasitic infection. In fact, our findings suggest that activation of host PTP SHP-1 in response to Leishmania infection tames an excessive inflammatory response that would otherwise be detrimental for the parasite.…”

Section: Discussionmentioning

confidence: 84%

“…SHP-1 deficiency is known to provoke dermal infiltration of inflammatory cells, mainly neutrophils [25]. These cells, recognized for their important antimicrobial activity, have been shown to be essential to minimize parasite progression in the early steps of Lm infection [18,33]. They are also important in the clearance of L. donovani from the liver and spleen of B cell-deficient mice [36].…”

Section: Discussionmentioning

confidence: 99%

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Regulation of theLeishmania-induced innate inflammatory response by the protein tyrosine phosphatase SHP-1

et al. 2005

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Modulation of the phagocyte protein tyrosine phosphatase (PTP) SHP-1 by the parasite Leishmania favors its survival and propagation within its mammalian host. In vivo, the absence of SHP-1 leads to virtually absent footpad swelling, accompanied by enhanced inducible nitric oxide synthase expression. In this study, using an air pouch model, we show that viable motheaten SHP-1-deficient mice harbored a stronger inflammatory response against Leishmania infection than wild-type mice. This response was portrayed by higher pro-inflammatory cytokine (TNF-a, IL-1b and IL-6) expression and secretion and by greater chemokine and chemokine receptor expression. These inflammatory molecules were probably responsible for the stronger cellular recruitment, mainly of neutrophils, seen at the site of infection in viable motheaten mice within 6 h post inoculation. We also provide strong evidence that protein tyrosine phosphatases in general, and SHP-1 in particular, are important regulators of chemokine gene expression. Overall, this study suggests that the ability of Leishmania to induce SHP-1 activity in its host allows the taming of an otherwise strong innate inflammatory response that would be detrimental for its survival and progression.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Regulation of theLeishmania-induced innate inflammatory response by the protein tyrosine phosphatase SHP-1

et al. 2005

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“…It has been previously shown that neutrophils play a critical role in controlling L. major (9) and Leishmania donovani infection (23). Upon inoculation of Lb promastigotes into the ear dermis of BALB/c mice, neutrophils can be detected throughout the duration of clinical disease (14).…”

Section: In Vivo Neutrophil Depletion Enhances Parasite Growth While mentioning

confidence: 99%

“…In resistant mice, transient depletion of neutrophils has been shown to lead to an increase in the parasite load (8,9). However, neutrophil depletion in susceptible mice (BALB/c) has been shown to lead to the opposite effect, as demonstrated by an increase in parasite elimination (10,11).…”

mentioning

confidence: 99%

Neutrophils and Macrophages Cooperate in Host Resistance againstLeishmania braziliensisInfection

Novais

Santiago²,

Báfica³

et al. 2009

The Journal of Immunology

132

121

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Neutrophils play an active role in the control of infections caused by intracellular pathogens such as Leishmania. In the present study, we investigated the effect of neutrophil depletion at the time of Leishmania braziliensis infection of BALB/c mice and how neutrophils interact with the infected macrophage to promote parasite elimination. The in vivo depletion of neutrophils led to a significant increase in parasite load and enhanced the Th1-Th2 immune response in this experimental model of infection. BALB/c mice coinoculated with both parasites and live neutrophils displayed lower parasite burdens at the site of infection and in the draining lymph nodes. In vitro, we observed that live neutrophils significantly reduced the parasite load in L. braziliensis-infected murine macrophages, an effect not observed with Leishmania major. L. braziliensis elimination was dependent on the interaction between neutrophils and macrophages and was associated with TNF-α as well as superoxide production. Furthermore, cooperation between neutrophils and macrophages toward parasite elimination was also observed in experiments performed with L. braziliensis-infected human cells and, importantly, with two other New World Leishmania species. These results indicate that neutrophils play an important and previously unappreciated role in L. braziliensis infection, favoring the induction of a protective immune response.

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“…According to Aga et al (10), these cells have their survival time increased by the inhibition of apoptosis induced by Leishmania parasite, predisposing them to serve as hosts to the parasites in the initial phase of infection. Lima et al (11) have already reported that neutrophils present a leishmanicidal activity by holding back the spread of the parasite at the beginning of the infection. However, the precise immunoregulatory role of PMN infected with Leishmania is not completely understood.…”

Section: Introductionmentioning

confidence: 98%

Cell migration induced by Leishmania (Leishmania) amazonensis, Leishmania (Leishmania) major and Leishmania (Viannia) braziliensis into the peritoneal cavity of BALB/c mice

Wakimoto¹,

Gaspareto²,

Silveira³

et al. 2010

J. Venom. Anim. Toxins incl. Trop. Dis

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In American cutaneous leishmaniasis, the initial infection phase is characterized by recruitment of neutrophils and monocytes. The migration of these cells in response to the presence of Leishmania in the peritoneum of affected animals remains unclear. The objective of this study was to investigate cell migration to the peritoneum of BALB/c mice after infection with Leishmania (Leishmania) amazonensis, Leishmania (Viannia) braziliensis and Leishmania (Leishmania) major. Initially, Leishmania spp. was intraperitoneally inoculated in five groups of six animals each and the cell migration was analyzed 0, 3, 6, 12, 24 and 48 hours after infection. Different cell counts were performed with a staining kit and showed a higher percentage of polymorphonuclear than mononuclear cells in all three species studied. The total cell count revealed peak migration in L. (L.) amazonensis and L. (L.) major at six hours, and in L. (V.) braziliensis at 12 hours. These results suggest that factors released from different cell types probably act by attracting polymorphonuclear cells, with the peak migration most likely depending on the species of Leishmania inoculated into the host

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The role of polymorphonuclear leukocytes in the resistance to cutaneous Leishmaniasis

Cited by 73 publications

References 28 publications

Regulation of theLeishmania-induced innate inflammatory response by the protein tyrosine phosphatase SHP-1

Regulation of theLeishmania-induced innate inflammatory response by the protein tyrosine phosphatase SHP-1

Neutrophils and Macrophages Cooperate in Host Resistance againstLeishmania braziliensisInfection

Cell migration induced by Leishmania (Leishmania) amazonensis, Leishmania (Leishmania) major and Leishmania (Viannia) braziliensis into the peritoneal cavity of BALB/c mice

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