Type 1 and type 2 responses to Leishmania major

Rogers, Kathleen A.

doi:10.1016/s0378-1097(02)00470-6

Cited by 49 publications

(68 citation statements)

References 30 publications

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“…It was also shown that the CD28/ CD80-CD86 interaction on neutrophil/macrophages induces IFN-␥ production, restricting the growth of L. major (44). Importantly, the mechanisms leading to cure and resistance to Leishmania infection are associated with macrophage activation, resulting from TNF-␣-and IFN-␥-induced production of free radicals and ultimately with destruction of the intracellular parasites (45,46).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…The cutaneous leishmaniasis laboratory mouse model using C57BL/6 (resistant) and BALB/c (susceptible) infected with L. major is the most employed system for analyzing the regulation of the immune response against this pathogen only contained by a cell-mediated response 19,30 . However, C57BL/6 mice inoculated with L. (L.) mexicana developed a chronic disease 2 .…”

Section: Introductionmentioning

confidence: 99%

Preliminary study towards a novel experimental model to study localized cutaneous leishmaniasis caused bY Leishmania (Leishmania) mexicana

Sosa-Bibiano

Wynsberghe

Canto-Lara

et al. 2012

Rev. Inst. Med. trop. S. Paulo

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SUMMARYThere is not an experimental model of localized cutaneous leishmaniasis (LCL) caused by Leishmania (Leishmania) mexicana. The aim of the present study was to characterize the clinical and histological features of Peromyscus yucatanicus experimentally infected with L. (L.) mexicana. A total of 54 P. yucatanicus (groups of 18) were inoculated with 1x10 6 promastigotes of L. (L.) mexicana in the base of the tail. They were euthanized at three and six months post experimental infection. The control group was inoculated with RPMI-1640. The predominant clinical sign observed was a single ulcerated lesion in 27.77% (5/18) and in 11.11% (2/18) P. yucatanicus at three and six months respectively. The histological pattern described as chronic granulomatous inflammation with or without necrosis was found in 7/7 (100%) biopsies of euthanized P. yucatanicus at three (n = 5) and six (n = 2) months, respectively. These results resembled clinical and histological features caused by L. (L.) mexicana in humans, and support the possibility to employ P. yucatanicus as a novel experimental model to study LCL caused by this parasite.

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“…The inability of macrophages to kill the parasite is a result of the parasite's longreported capacity in skewing the host immune response toward a disease-promoting Th2 phenotype that consequently suppresses host-protective Th1 phenotype (15,16). To execute this, Leishmania needs specific molecules that are secreted by Leishmania itself or it may activate macrophages to produce immunosuppressive molecules that render the macrophage defense inactive.…”

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confidence: 99%

Prostaglandin E2 Negatively Regulates the Production of Inflammatory Cytokines/Chemokines and IL-17 in Visceral Leishmaniasis

Saha

Biswas

Srivastav

et al. 2014

The Journal of Immunology

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Persistence of intracellular infection depends on the exploitation of factors that negatively regulate the host immune response. In this study, we elucidated the role of macrophage PGE2, an immunoregulatory lipid, in successful survival of Leishmania donovani, causative agent of the fatal visceral leishmaniasis. PGE2 production was induced during infection and resulted in increased cAMP level in peritoneal macrophages through G protein–coupled E-series prostanoid (EP) receptors. Among four different EPs (EP1–4), infection upregulated the expression of only EP2, and individual administration of either EP2-specific agonist, butaprost, or 8-Br–cAMP, a cell-permeable cAMP analog, promoted parasite survival. Inhibition of cAMP also induced generation of reactive oxygen species, an antileishmanial effector molecule. Negative modulation of PGE2 signaling reduced infection-induced anti-inflammatory cytokine polarization and enhanced inflammatory chemokines, CCL3 and CCL5. Effect of PGE2 on cytokine and chemokine production was found to be differentially modulated by cAMP-dependent protein kinase A (PKA) and exchange protein directly activated by cAMP (EPAC). PGE2-induced decreases in TNF-α and CCL5 were mediated specifically by PKA, whereas administration of brefeldin A, an EPAC inhibitor, could reverse decreased production of CCL3. Apart from modulating inflammatory/anti-inflammatory balance, PGE2 inhibited antileishmanial IL-17 cytokine production in splenocyte culture. Augmented PGE2 production was also found in splenocytes of infected mice, and administration of EP2 antagonist in mice resulted in reduced liver and spleen parasite burden along with host-favorable T cell response. These results suggest that Leishmania facilitates an immunosuppressive environment in macrophages by PGE2-driven, EP2-mediated cAMP signaling that is differentially regulated by PKA and EPAC.

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Type 1 and type 2 responses to Leishmania major

Cited by 49 publications

References 30 publications

Neutrophils and Macrophages Cooperate in Host Resistance againstLeishmania braziliensisInfection

Neutrophils and Macrophages Cooperate in Host Resistance againstLeishmania braziliensisInfection

Preliminary study towards a novel experimental model to study localized cutaneous leishmaniasis caused bY Leishmania (Leishmania) mexicana

Prostaglandin E2 Negatively Regulates the Production of Inflammatory Cytokines/Chemokines and IL-17 in Visceral Leishmaniasis

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