Indigenous microbiota and Leishmaniasis

Lopes, Monalisa; Carneiro, Mariângela; Santos, Liliane Martins dos; Vieira, Leda Quércia

doi:10.1111/pim.12279

Cited by 22 publications

(17 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Commensal skin bacteria have been shown to influence the host-parasite interaction and pathology in models of cutaneous leishmaniasis (CL). Specifically, germ-free mice inoculated with L. major or L. amazonensis have been reported to develop smaller skin lesions [18][19][20], although others have observed larger lesions [21]. These data generally support a pro-inflammatory function for the microbiota in CL.…”

Section: Introductionmentioning

confidence: 78%

Fatal progression of experimental visceral leishmaniasis is associated with intestinal parasitism and secondary infection by commensal bacteria, and is delayed by antibiotic prophylaxis

Lewis¹,

Paun²,

Romano³

et al. 2020

PLoS Pathog

View full text Add to dashboard Cite

Leishmania donovani causes visceral leishmaniasis (VL), which is typically fatal without treatment. There is substantial variation between individuals in rates of disease progression, response to treatment and incidence of post-treatment sequelae, specifically post-kala-azar dermal leishmaniasis (PKDL). Nevertheless, the majority of infected people are asymptomatic carriers. Hamsters and mice are commonly used as models of fatal and non-fatal VL, respectively. Host and parasite genetics are likely to be important factors, but in general the reasons for heterogeneous disease presentation in humans and animal models are poorly understood. Host microbiota has become established as a factor in cutaneous forms of leishmaniasis but this has not been studied in VL. We induced intestinal dysbiosis in mice and hamsters by long-term treatment with broad-spectrum antibiotics in their drinking water. There were no significant differences in disease presentation in dysbiotic mice. In contrast, dysbiotic hamsters infected with L. donovani had delayed onset and progression of weight loss. Half of control hamsters had a rapid progression phenotype compared with none of the ABX-treated animals and the nine-month survival rate was significantly improved compared to untreated controls (40% vs. 10%). Antibiotic-treated hamsters also had significantly less severe hepatosplenomegaly, which was accompanied by a distinct cytokine gene expression profile. The protective effect was not explained by differences in parasite loads or haematological profiles. We further found evidence that the gut-liver axis is a key aspect of fatal VL progression in hamsters, including intestinal parasitism, bacterial translocation to the liver, malakoplakia and iron sequestration, none of which occurred in non-progressing murine VL. Diverse bacterial genera were cultured from VL affected livers, of which

show abstract

Section: Introductionmentioning

confidence: 78%

Fatal progression of experimental visceral leishmaniasis is associated with intestinal parasitism and secondary infection by commensal bacteria, and is delayed by antibiotic prophylaxis

Lewis¹,

Paun²,

Romano³

et al. 2020

PLoS Pathog

View full text Add to dashboard Cite

show abstract

“…Some authors have linked microbiota differences to subsequent variation in brain activity and changes in social behavior, a concept referred to as the gut-brain axis (e.g., Foster and McVey Neufeld, 2013;Mayer et al, 2015;Gacias et al, 2016) which is proposed to depend on several factors, including the immune system. Variation in microbiota is known to influence both local and systemic immune function by altering the balance of Th1/Th2 cell composition, influencing re-localization of neutrophils, or affecting macrophage polarization Lopes et al, 2016). Taken together, it is therefore not surprising that differences in microbiota can have a substantial impact on protozoan parasite infections in the gut and elsewhere.…”

Section: Microbiota As a General Confounder For Rodent Experimentsmentioning

confidence: 99%

Translational Rodent Models for Research on Parasitic Protozoa—A Review of Confounders and Possibilities

Ehret

Torelli

Klotz

et al. 2017

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Rodents, in particular Mus musculus, have a long and invaluable history as models for human diseases in biomedical research, although their translational value has been challenged in a number of cases. We provide some examples in which rodents have been suboptimal as models for human biology and discuss confounders which influence experiments and may explain some of the misleading results. Infections of rodents with protozoan parasites are no exception in requiring close consideration upon model choice. We focus on the significant differences between inbred, outbred and wild animals, and the importance of factors such as microbiota, which are gaining attention as crucial variables in infection experiments. Frequently, mouse or rat models are chosen for convenience, e.g., availability in the institution rather than on an unbiased evaluation of whether they provide the answer to a given question. Apart from a general discussion on translational success or failure, we provide examples where infections with single-celled parasites in a chosen lab rodent gave contradictory or misleading results, and when possible discuss the reason for this. We present emerging alternatives to traditional rodent models, such as humanized mice and organoid primary cell cultures. So-called recombinant inbred strains such as the Collaborative Cross collection are also a potential solution for certain challenges. In addition, we emphasize the advantages of using wild rodents for certain immunological, ecological, and/or behavioral questions. The experimental challenges (e.g., availability of species-specific reagents) that come with the use of such non-model systems are also discussed. Our intention is to foster critical judgment of both traditional and newly available translational rodent models for research on parasitic protozoa that can complement the existing mouse and rat models.

show abstract

“…It is known that parasite strain, genetically or environmentally determined host immune response, and vector components all contribute [ 3 , 34 , 35 , 36 ]. Further investigation is needed to define the contributions of host genetics and microbiota to the cutaneous manifestations of leishmaniasis [ 37 , 38 , 39 , 40 ].…”

Section: Introductionmentioning

confidence: 99%

Cutaneous Manifestations of Human and Murine Leishmaniasis

Scorza

Carvalho

Wilson

2017

IJMS

157

119

View full text Add to dashboard Cite

The leishmaniases are diseases caused by pathogenic protozoan parasites of the genus Leishmania. Infections are initiated when a sand fly vector inoculates Leishmania parasites into the skin of a mammalian host. Leishmania causes a spectrum of inflammatory cutaneous disease manifestations. The type of cutaneous pathology is determined in part by the infecting Leishmania species, but also by a combination of inflammatory and anti-inflammatory host immune response factors resulting in different clinical outcomes. This review discusses the distinct cutaneous syndromes described in humans, and current knowledge of the inflammatory responses associated with divergent cutaneous pathologic responses to different Leishmania species. The contribution of key hematopoietic cells in experimental cutaneous leishmaniasis in mouse models are also reviewed and compared with those observed during human infection. We hypothesize that local skin events influence the ensuing adaptive immune response to Leishmania spp. infections, and that the balance between inflammatory and regulatory factors induced by infection are critical for determining cutaneous pathology and outcome of infection.

show abstract

Indigenous microbiota and Leishmaniasis

Cited by 22 publications

References 89 publications

Fatal progression of experimental visceral leishmaniasis is associated with intestinal parasitism and secondary infection by commensal bacteria, and is delayed by antibiotic prophylaxis

Fatal progression of experimental visceral leishmaniasis is associated with intestinal parasitism and secondary infection by commensal bacteria, and is delayed by antibiotic prophylaxis

Translational Rodent Models for Research on Parasitic Protozoa—A Review of Confounders and Possibilities

Cutaneous Manifestations of Human and Murine Leishmaniasis

Contact Info

Product

Resources

About