Humoral and cellular immune responses in dogs with inapparent natural Leishmania infantum infection

Coura‐Vital, Wendel; Marques, Marcos José; Giunchetti, Rodolfo Cordeiro; Teixeira-Carvalho, Andréa; Moreira, Nádia das Dores; Vitoriano-Souza, Juliana; Vieira, Paula Melo Abreu; Carneiro, Cláudia Martins; Corrêa-Oliveira, Rodrigo; Martins‐Filho, Olindo Assis; Carneiro, Mariângela; Reis, Alexandre Barbosa

doi:10.1016/j.tvjl.2011.04.005

Cited by 36 publications

(53 citation statements)

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“…However, it is worth noting that despite a report of two dogs infected with Leishmania (L.) amazonensis in the municipality of Araçatuba, no cases of human disease nor the natural vector of this parasite species has been described in this region to date [17]. The immunohistochemical quantitative studies in lymph nodes or in spleens did not show significant differences ( P = 0.2471 and P = 0.5158, respectively) between the clinical groups, supporting the idea that our infected asymptomatic dogs could be in the pre-patent period of infection, as reported by Coura-Vital et al [16]. Figure 1A shows the number of parasites/mm 2 in the popliteal lymph nodes and spleens of symptomatic and asymptomatic dogs.…”

Section: Resultssupporting

confidence: 83%

“…Thus, transversal studies related to natural infection in dogs can generate controversial results, especially when animals are sorted in clinical groups, since asymptomatic clinical status can represent a resistance pole, but also an early phase of infection or a pre-patent disease period [15]. Two populations of asymptomatic dogs in endemic areas has been characterized: one seronegative, but with positive molecular detection of L. (L.) infantum chagasi , and another with positive serology and molecular results for the parasite, suggesting that asymptomatic dogs have a dichotomous infection spectrum that can influence humoral and cellular immunological status during CVL infection [16]. …”

Section: Resultsmentioning

confidence: 99%

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Expression of inducible nitric oxide synthase in macrophages inversely correlates with parasitism of lymphoid tissues in dogs with visceral leishmaniasis

et al. 2014

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BackgroundThere are only a few studies reporting the role of nitric oxide metabolites for controlling macrophage intracellular parasitism, and these are controversial. Therefore, the present study aimed to evaluate the expression of inducible nitric oxide synthase (iNOS) in the lymph nodes and spleen of dogs affected by visceral leishmaniasis through immunohistochemistry and to determine its correlation with tissue parasite burden and serum interferon (IFN)-γ levels. Twenty-eight dogs were selected and assigned to one of two groups, symptomatic (n = 18) and asymptomatic (n = 10), according to clinical status and laboratory evaluation. A negative control group (n = 6) from a non-endemic region for visceral leishmaniasis was included as well.ResultsParasite density (amastigotes/mm2) was similar between clinical groups in the lymph nodes (P = 0.2401) and spleen (P = 0.8869). The density of iNOS+ cells was higher in infected dogs compared to controls (P < 0.05), without a significant difference in lymph node (P = 0.3257) and spleen (P = 0.5940) densities between symptomatic and asymptomatic dogs. A positive correlation was found between the number of iNOS+ cells in lymph nodes and interferon-γ levels (r = 0.3776; P = 0.0303), and there was a negative correlation between parasites and iNOS+ cell densities both in lymph nodes (r = −0.5341; P = 0.0034) and spleen (r = −0.4669; P = 0.0329).ConclusionThe negative correlation observed between tissue parasitism and the expression of iNOS may be a reflection of NO acting on the control of parasites.

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Section: Resultssupporting

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Expression of inducible nitric oxide synthase in macrophages inversely correlates with parasitism of lymphoid tissues in dogs with visceral leishmaniasis

et al. 2014

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“…The difference between IFN-γ and L-10 explained the differences in parasite load between organs. A recent study carried out by Coura-Vital and co-workers [34], showed that asymptomatic dogs had a higher frequency of CD4 and CD8 T cells, these cells are the main producer of IFN-γ and TNF-α, which may lead to parasite control and maintenance of asymptomatic status. …”

Section: Discussionmentioning

confidence: 99%

Association of Pro-Inflammatory Cytokines and Iron Regulatory Protein 2 (IRP2) with Leishmania Burden in Canine Visceral Leishmaniasis

et al. 2013

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Leishmania infantum infection in humans and dogs can evolve with a wide range of clinical presentations, varying from asymptomatic infections to visceral leishmaniasis. We hypothesized that the immune response elicited by L. infantum infection could modulate whether the host will remain asymptomatic or progress to disease. A total of 44 dogs naturally infected with L. infantum were studied. Leishmania burden was estimated in the blood and spleen by qPCR. The expression of IFN-γ, TNF-α, IL-10 and Iron Regulatory Protein 2 (IRP2) were determined in the spleen by quantitative PCR. Sera cytokines were evaluated by ELISA. Dogs were grouped in quartiles according parasite burden. Increased expression of IFN-γ and TNF-α was associated with reduced Leishmania burden, whereas increased IL-10 and IRP2 expressions were associated with higher Leishmania load. Increased plasma albumin and IFN-γ expression explained 22.8% of the decrease in parasite burden in the spleen. These data confirm that lower IFN-γ response and higher IL-10 correlated with increased parasite load and severity of the visceral leishmaniasis in dogs. The balance between the branches of immune response and the intracellular iron availability could determine, in part, the course of Leishmania infection.

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“…Such phenomena are relatively common during Leishmania infection and may be related to the chronic phase of the disease (22,23).…”

Section: Infantum Upregulates Tlr9 Expression During Infectionmentioning

confidence: 99%

Toll-Like Receptor 9 Signaling in Dendritic Cells Regulates Neutrophil Recruitment to Inflammatory Foci following Leishmania infantum Infection

et al. 2015

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Leishmania infantum is a protozoan parasite that causes visceral leishmaniasis (VL). This infection triggers dendritic cell (DC)activation through the recognition of microbial products by Toll-like receptors (TLRs). Among the TLRs, TLR9 is required for DC activation by different Leishmania species. We demonstrated that TLR9 is upregulated in vitro and in vivo during infection. We show that C57BL/6 mice deficient in TLR9 expression (TLR9 ؊/؊ mice) are more susceptible to infection and display higher parasite numbers in the spleen and liver. The increased susceptibility of TLR9 ؊/؊ mice was due to the impaired recruitment of neutrophils to the infection foci associated with reduced levels of neutrophil chemoattractants released by DCs in the target organs. Moreover, both Th1 and Th17 cells were also committed in TLR9 ؊/؊ mice. TLR9-dependent neutrophil recruitment is mediated via the MyD88 signaling pathway but is TIR domain-containing adapter-inducing interferon beta (TRIF) independent. Furthermore, L. infantum failed to activate both plasmacytoid and myeloid DCs from TLR9 ؊/؊ mice, which presented reduced surface costimulatory molecule expression and chemokine release. Interestingly, neutrophil chemotaxis was affected both in vitro and in vivo when DCs were derived from TLR9 ؊/؊ mice. Our results suggest that TLR9 plays a critical role in neutrophil recruitment during the protective response against L. infantum infection that could be associated with DC activation. L eishmania intracellular protozoan parasites cause a heterogeneous disease that can range from cutaneous lesions to visceral disease. Visceral disease can be caused by both Leishmania donovani and Leishmania infantum and is the most severe manifestation of this type of parasite infection. Therefore, Leishmania infections remain an important cause of human mortality and morbidity around the world (www.paho.org/english/ad/dpc/cd /res-dch-leish-priorities.pdf).Host defenses against Leishmania spp. depend on the activation of an inflammatory response initiated by the innate immune system (1), followed by specific immune responses mediated by gamma interferon (IFN-␥)-or interleukin-17 (IL-17)-producing CD4 ϩ T lymphocytes (2, 3). The innate immune system has specific mechanisms to rapidly recognize the parasite. A major component of pathogen recognition comprises a family of Toll-like receptors (TLRs) that detect common pathogen-associated molecular patterns (PAMPs) of various groups of microorganisms (4-7), including Leishmania spp. (8, 9).The role of TLRs in Leishmania infection control has been supported by the observations that mice lacking MyD88, an adaptor molecule required for TLR signaling, display enhanced susceptibility to infection (10, 11). It has been described that resistance to Leishmania species infection is dependent on parasite lipophosphoglycan (LPG) recognition by TLR2 (8), the induction of IL-12, and the development of a Th1 immune response (12) together with NO production (13). Previous studies demonstrated a role for TLR2 and TLR3 i...

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Humoral and cellular immune responses in dogs with inapparent natural Leishmania infantum infection

Cited by 36 publications

References 36 publications

Expression of inducible nitric oxide synthase in macrophages inversely correlates with parasitism of lymphoid tissues in dogs with visceral leishmaniasis

Expression of inducible nitric oxide synthase in macrophages inversely correlates with parasitism of lymphoid tissues in dogs with visceral leishmaniasis

Association of Pro-Inflammatory Cytokines and Iron Regulatory Protein 2 (IRP2) with Leishmania Burden in Canine Visceral Leishmaniasis

Toll-Like Receptor 9 Signaling in Dendritic Cells Regulates Neutrophil Recruitment to Inflammatory Foci following Leishmania infantum Infection

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