Plasmodium berghei ANKA infection results in exacerbated immune responses from C57BL/6 mice displaying hypothalamic obesity

Carvalho, Roberto Gameiro de; Soares, Sara Malaguti Andrade; Gualberto, Ana Cristina Moura; Evangelista, Gabriela Coeli Menezes; Duque, Juliane Aparecida Marinho; Ferreira, Ana Paula; Macedo, Gilson Costa; Gameiro, Jacy

doi:10.1016/j.cyto.2015.01.025

Cited by 11 publications

(11 citation statements)

References 17 publications

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“…It is important to highlight that, in vivo, Leishmania parasites activate the inflammasome without the requirement of priming or LPS injection . We believe that this occur because of tissue damage caused during infection, the release of alarmins, such as ATP, IL‐1α, and high mobility group box 1 (HMGB1), and also other inflammatory mediators such as IFN‐γ and TNF‐α, which can boost NF‐κB signaling and are extremely important in the pathogenesis of Leishmania infections . In addition, it is also possible that bacterial co‐infection in the cutaneous Leishmania lesions present in patients favor the priming of myeloid cells during Leishmania infections in vivo.…”

Section: Discussionmentioning

confidence: 99%

Macrophage priming is dispensable for NLRP3 inflammasome activation and restriction of Leishmania amazonensis replication

Carvalho

Silva

Santos

et al. 2019

Journal of Leukocyte Biology

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The NLRP3 inflammasome is activated in response to multiple stimuli and triggers activation of caspase‐1 (CASP1), IL‐1β production, and inflammation. NLRP3 activation requires two signals. The first leads to transcriptional regulation of specific genes related to inflammation, and the second is triggered when pathogens, toxins, or specific compounds damage cellular membranes and/or trigger the production of reactive oxygen species (ROS). Here, we assess the requirement of the first signal (priming) for the activation of the NLRP3 inflammasome in bone marrow‐derived macrophages (BMDMs) infected with Leishmania amazonensis. We found that BMDMs express the inflammasome components NLRP3, ASC, and CASP1 at sufficient levels to enable the assembly and activation of NLRP3 inflammasome in response to infection. Therefore, priming was not required for the formation of ASC specks, CASP1 activation (measured by fluorescent dye FAM‐YVAD), and restriction of L. amazonensis replication via the NLRP3 inflammasome. By contrast, BMDM priming was required for CASP1 cleavage (p20) and IL‐1β secretion, because priming triggers robust up‐regulation of pro‐IL‐1β and CASP11 that are important for efficient processing of CASP1 and IL‐1β. Taken together, our data shed light into the cellular and molecular processes involved in activation of the NLRP3 in macrophages by Leishmania, a process that is important for the outcome of Leishmaniasis.

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Section: Discussionmentioning

confidence: 99%

Macrophage priming is dispensable for NLRP3 inflammasome activation and restriction of Leishmania amazonensis replication

Carvalho

Silva

Santos

et al. 2019

Journal of Leukocyte Biology

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“…Obese mice did not show overproduction of proinflammatory cytokines by cells from the draining lymph nodes. In response to parasite antigens, it was expected a higher production of pro-inflammatory cytokines by obese mice, as it was observed for infection with Plasmodiun berguei [19] and also for infection with Leishmania chagasi [22].…”

Section: Discussionmentioning

confidence: 80%

“…Interestingly, diet-induced obesity in C57BL/6 mice was protective in a model of cerebral malaria [18]. Hypothalamic obesity in C57BL/6 mice infected with Plasmodium berghei ANKA resulted in decreased parasitemia, but exacerbated inflammation, and increased mortality rate [19]. Leptin-deficient obese mice (ob/ob mice) are also more susceptible to Trypanosoma cruzi infection [20,21].…”

Section: Introductionmentioning

confidence: 99%

Obesity impairs resistance to Leishmania major infection in C57BL/6 mice

et al. 2020

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An association between increased susceptibility to infectious diseases and obesity has been described as a result of impaired immunity in obese individuals. It is not clear whether a similar linkage can be drawn between obesity and parasitic diseases. To evaluate the effect of obesity in the immune response to cutaneous Leishmania major infection, we studied the ability of C57BL/6 mice fed a hypercaloric diet (HSB) to control leishmaniasis. Mice with diet-induced obesity presented thicker lesions with higher parasite burden and a more intense inflammatory infiltrate in the infected ear after infection with L. major. There was no difference between control and obese mice in IFN-gamma or IL-4 production by auricular draining lymph node cells, but obese mice produced higher levels of IgG1 and IL-17. Peritoneal macrophages from obese mice were less efficient to kill L. major when infected in vitro than macrophages from control mice. In vitro stimulation of macrophages with IL-17 decreased their capacity to kill the parasite. Moreover, macrophages from obese mice presented higher arginase activity. To confirm the role of IL-17 in the context of obesity and infection, we studied lesion development in obese IL-17R-/-mice infected with L. major and found no difference in skin lesions and the leukocyte accumulation in the draining lymph node is redcuced in knockout mice compared between obese and lean animals. Our results indicate that diet-induced obesity impairs resistance to L. major in C57BL/6 mice and that IL-17 is involved in lesion development.

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“…Obese mice did not show overproduction of proinflammatory cytokines by cells from the draining lymph nodes. It was expected a higher production of TNF-α and IFN-γ in obese mice with in response to parasite antigens, as it was observed for infection with Plasmodiun berguei (45) and also for infection with Leishmania chagasi (23) in obese C57BL/6 mice. However, obesity did not interfere with TNF-α and IFN-γ levels in our study.…”

Section: Discussionmentioning

confidence: 90%

“…Interestingly, diet-induced obesity in C57BL/6 mice was protective in a model of cerebral malaria (19). Hypothalamic obesity in C57BL/6 mice infected with Plasmodium berghei ANKA resulted in decreased parasitemia, but exacerbated inflammation, and increased mortality rate (20). Leptin-deficient obese mice (ob/ob mice) are also more susceptible to Trypanosoma cruzi infection (21,22).…”

Section: Introductionmentioning

confidence: 99%

Obesity impairs resistance toLeishmania majorinfection in C57BL/6 mice

Maioli

Silva

Martins

et al. 2018

Preprint

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23An association between increased susceptibility to infectious diseases and obesity has been 24 described as a result of impaired immunity in obese individuals. It is not clear whether a similar 25 linkage can be drawn between obesity and parasitic diseases. To evaluate the effect of obesity 26 in the immune response to cutaneous L. major infection, we studied the ability of C57BL/6 mice 27 submitted to a high fat and sugar diet to control leishmaniasis. Mice with diet-induced obesity 28 presented thicker lesions with higher parasite burden and more inflammatory infiltrate in the 29 infected ear when infected with L. major. We observe no difference in IFN-γ or IL-4 production 30 by draining lymph node cells between control and obese mice, but obese mice presented 31 higher production of IgG1 and IL-17. A higher percentage of in vitro-infected peritoneal 32 macrophages was found when these cells were obtained from obese mice when compared to 33 lean mice. In vitro stimulation of macrophages with IL-17 decreased the capacity of cells from 34 control mice to kill the parasite. Moreover, macrophages from obese mice presented higher 35 arginase activity. Together our results indicate that diet-induced obesity impairs resistance to L. 36 major in C57BL/6 mice without affecting the development of Th1 response. 37 38 39 4 40 Author Summary 41The obesity is a public health problem and it is reaching extraordinary numbers in the world 42 and others diseases are being involved and aggravated as consequence of obesity. What we 43 know is that some diseases are more severe in obese people than in normal people. We did not 44 know how obesity changes the profile of immune response to infectious agents, leading to the 45 more severe diseases. That`s why we decided to investigate how obese mice lead with 46 Leishmania major infection. Leishmaniasis is a protozoa parasite infection considered a 47 neglected disease. To try our hypothesis we gave a hipercaloric diet to induce obesity in 48 C57BL/6 mice. After that, we injected L. major in the mice ear and followed the lesion for 8 49 weeks. We observed a ticker lesion and the cells from draining lymph node from obese mice 50 produced more IL-17 than cells from normal mice. We also infected in vitro, macrophages from 51 obese mice and stimulated the cells with IL-17, and we observed that the macrophages from 52 obese mice are more infected by the L. major and it is worst in the presence of IL-17. Our 53 results suggest that diet induced obesity decrease the resistance to infection. 54 55 157 20 °C. 158 159 Histology

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Plasmodium berghei ANKA infection results in exacerbated immune responses from C57BL/6 mice displaying hypothalamic obesity

Cited by 11 publications

References 17 publications

Macrophage priming is dispensable for NLRP3 inflammasome activation and restriction of Leishmania amazonensis replication

Macrophage priming is dispensable for NLRP3 inflammasome activation and restriction of Leishmania amazonensis replication

Obesity impairs resistance to Leishmania major infection in C57BL/6 mice

Obesity impairs resistance toLeishmania majorinfection in C57BL/6 mice

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