Research paper
Systemic and compartmentalized immune response in canine visceral leishmaniasis

https://doi.org/10.1016/j.vetimm.2008.10.307Get rights and content

Abstract

Human visceral leishmaniasis (VL) and canine visceral leishmaniasis (CVL) are the most important emerging diseases with high prevalence in Latin American countries and are mainly caused by Leishmania (L.) chagasi (Syn = L. infantum). CVL has a great impact on Brazilian public health because domestic dogs are the most important VL peri-domicile reservoirs in both urban and peri-urban areas. Our findings highlight the complexity of cellular immunological events related to the natural infection from dogs by L. chagasi, additionally correlating major peripheral blood phenotypic markers with clinical status and tissues parasite density. Our main results demonstrated that lower frequency of circulating B cells and monocytes are important markers of severe CVL, whereas increased levels of CD8+ lymphocytes appear to be the major phenotypic feature of asymptomatic disease. Determination of the isotypes patterns during CVL demonstrated that asymptomatic dogs and those with low parasitism are associated with an increase of IgG1, while the symptomatic dogs and those with high parasitism are associated with an increase of IgG, IgG2, IgM, IgA and IgE immunoglobulins. Pioneer findings obtained by our group showed a correlation between clinical status of CVL with degree of tissue parasite density. This data demonstrated that asymptomatic dogs presented low parasitism while symptomatic dogs are associated with high parasite load in various tissues such as skin, bone marrow and spleen. We have also investigated the association between tissue parasitism and CVL clinical forms. Regardless of clinical status, skin and spleen are the major sites of high parasite density during ongoing CVL. Furthermore, we demonstrated that bone marrow and spleen parasite density are the most reliable parasitological markers to decode the clinical status of CVL. In this article, we have reviewed some aspects of the histopathological and immunological events occurring in natural and experimental L. chagasi/L. infantum infection, pointing out the main L. chagasi-parasitized tissue. We have discussed the importance of the association between parasite density, immunological/histopathological aspects and clinical status of the CVL, their current applications, challenges for the future and potential opportunities in CVL research.

Section snippets

Impact of canine control on the epidemiology from canine and human visceral leishmaniasis

Visceral leishmaniasis (VL) is one of the most important emerging diseases with high prevalence in Latin American countries (Tesh, 1995). VL and canine visceral leishmaniasis (CVL) are mainly caused by Leishmania (L.) chagasi (Syn = L. infantum) in South America and Europe (Mauricio et al., 2000). Peri-domestic sand flies acquire the etiological agent by feeding on infected wild/domestic reservoirs and transmit it, causing severe disease in humans (Tesh, 1995, WHO, 2000). Nowadays, VL is

Clinical and biochemical/hematological biomarkers of progression in CVL

Canine visceral leishmaniasis manifests itself as a broad clinical spectrum ranging from asymptomatic infection to patent severe disease, which mostly culminates in death (Reis et al., 2006b). According to Mancianti et al. (1988), asymptomatic dogs (AD) do not show visible clinical signs because they are apparently healthy animals (Fig. 1A), whereas oligosymptomatic dogs (OD) present some signs such as cutaneous ulcerations, frequently observed on the tip of the ears and on the periorbital

Tissues parasite load and clinical progression in CVL

Evaluation of parasite load by “leishman donovan units” (LDU), number of Leishmania amastigote by 1,000 nucleated cells (Stauber, 1955 modified by Reis et al., 2006a), and anti-Leishmania detection by immunohistochemistry are important parasitological tools to verify parasite density in different lymphoid compartments (Tafuri et al., 2001, Tafuri et al., 2004, Sanchez et al., 2004, Reis et al., 2006a, Reis et al., 2006b, Reis et al., 2006c, Giunchetti et al., 2006, Giunchetti et al., 2008a,

Systemic immunological biomarkers of clinical progression in CVL

In the last decade, various research groups have concentrated efforts studying immunopathology of dogs naturally and experimentally infected by L. chagasi/L. infantum (Cabral et al., 1992, Martinez-Moreno et al., 1993, Martinez-Moreno et al., 1995, Pinelli et al., 1994, Pinelli et al., 1995, Pinelli et al., 1999a, Pinelli et al., 1999b, Brandonisio et al., 1996, Bourdoiseau et al., 1997, Nieto et al., 1999, Alvar et al., 2004, Tafuri et al., 2004, Solano-Gallego et al., 2004, Solano-Gallego et

Compartmentalized immune response in different lymphoid organs in CVL

Analysis of the immune response in different compartments during chronic infection is a useful new scientific strategy for the study of the immune response in parasitic/infectious diseases. This approach allows simultaneous investigation of the immunological events observed in the peripheral blood and may indicate whether they are representative of those occurring in the lymphoid tissues (Teixeira-Carvalho et al., 2002).

Although CVL is known to be a severe systemic disease, there are a few

Conclusion and new challenges

Our findings highlight the complexity of cellular immunological events related to natural infection from dogs by L. chagasi, correlating major peripheral blood phenotypic markers with clinical status and tissues parasite density. Our data suggest that the sustained T cell compartment (both CD4+ and CD8+ T cells) observed in AD and LP groups may be resultant from the high activity of the host immune system to perform antigen presentation and to remove parasites from affected sites. Lower

Conflict of interest

None.

Acknowledgements

The authors wish to express their appreciation for the hard work carried out by the kennel staff of the Universidade Federal de Ouro Preto and Universidade Federal de Minas Gerais for their special dedication during the execution of this project. We also thank the people from Fundação Nacional da Saúde, Ministério da Saúde, Distrito Regional de Belo Horizonte, Minas Gerais, for their special dedication to this work. The authors are also grateful for the use of the facilities at CEBIO,

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