The role of chemokines in Schistosoma mansoni infection: insights from human disease and murine models

Souza, Adriano Lopes de; Sousa-Pereira, Sílvio Roberto; Teixeira, Mauro Martins; Lambertucci, José Roberto; Teixeira, Antônio Lúcio

doi:10.1590/s0074-02762006000900054

Cited by 12 publications

(12 citation statements)

References 39 publications

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“…CCR5 is one of the receptors for CCL3, a chemokine previously shown to play an important role in the pathogenesis of human and murine schistosomiasis (16,41,42,43). Here, we demonstrate that in the absence of CCR5, S. mansoni infection is severely deleterious to the host, as shown by an increase in mortality rates and egg-associated liver pathology.…”

Section: Discussionmentioning

confidence: 54%

“…The latter chemokine has been suggested by two previous studies of our group to play an important role in the pathogenesis of schistosomiasis. The main findings of these studies which led to this suggestion were (i) a correlation between high plasma levels of CCL3 and the occurrence of severe disease in humans (16,42) and (ii) the development of milder infection and pathology in CCL3 Ϫ/Ϫ mice than in wild-type (WT) controls (42,43). Moreover, treatment with Met-RANTES, a CCR1 and CCR5 antagonist, inhibited cellular reactivity in a model of in vitro granuloma reactions when cells were obtained from hepatosplenic patients, while it tended to exacerbate the granuloma index in cultures derived from intestinal patients (16).…”

mentioning

confidence: 99%

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Experimental Infection withSchistosoma mansoniin CCR5-Deficient Mice Is Associated with Increased Disease Severity, as CCR5 Plays a Role in Controlling Granulomatous Inflammation

Souza

Pereira

et al. 2011

Infect Immun

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The plasma level of the chemokine CCL3 is elevated in patients with chronic severe schistosomiasis mansoni. We have previously shown that CCL3؊/؊ mice with experimental infection showed diminished pathology and worm burden compared to those of wild-type (WT) mice. To elucidate further the role of CC chemokines during schistosomiasis mansoni infection, we evaluated the course of infection in C57BL/6J mice deficient in CCR5, one of the receptors for CCL3. The CCR5 deficiency proved to be remarkably deleterious to the host, since mortality rates reached 70% at 14 weeks postinfection in CCR5 ؊/؊ mice and 19% in WT mice. The increased lethality was not associated with an increased parasite burden, since similar numbers of eggs and adult worms were found in mice from both groups. Liver granulomas of chronically infected CCR5 ؊/؊ mice were larger and showed greater numbers of cells and collagen deposition than liver granulomas from WT mice. This was associated with higher levels of production of intereleukin-5 (IL-5), IL-13, CCL3, and CCL5 in infected CCR5 ؊/؊ mice than in infected WT mice. Moreover, at 8 weeks after infection, just before changes in pathology and mortality, the numbers of FoxP3-positive cells were lower in liver granulomas of CCR5 ؊/؊ mice than in WT mice. In conclusion, the CCR5 deletion is deleterious to mice infected with Schistosoma mansoni, and this is associated with enhanced fibrosis and granulomatous inflammation.

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Section: Discussionmentioning

confidence: 54%

mentioning

confidence: 99%

Experimental Infection withSchistosoma mansoniin CCR5-Deficient Mice Is Associated with Increased Disease Severity, as CCR5 Plays a Role in Controlling Granulomatous Inflammation

Souza

Pereira

et al. 2011

Infect Immun

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“…For example, in Chagas disease and schistosomiasis, a change in the expression of chemokine receptors on PBMCs has been associated with progression of the disease (22, 23). In the case of severe chronic chagasic cardiomyopathy, a serious complication of Trypanosoma cruzi infection, diminished CCR5 and CXCR4 expression on PBMCs of infected individuals was associated with the onset of heart failure (22).…”

Section: Discussionmentioning

confidence: 99%

“…In the case of severe chronic chagasic cardiomyopathy, a serious complication of Trypanosoma cruzi infection, diminished CCR5 and CXCR4 expression on PBMCs of infected individuals was associated with the onset of heart failure (22). In Schistosoma mansoni infections, unbalanced chemokine receptor activation with increased expression of CCR1 relative to CCR5 correlated with a severe form of the disease (23). Chemokine receptor expression can also be altered in viral infections such as chronic hepatitis C infection, in which reduced surface expression of CCR1 and CCR5 on peripheral blood CD8 + T lymphocytes results in lower CC chemokine responsiveness (24), which, in turn, may affect T cell recruitment to the infected liver, an important step in clearing the virus.…”

Section: Discussionmentioning

confidence: 99%

Expanded Numbers of Circulating Myeloid Dendritic Cells in Patent Human Filarial Infection Reflect Lower CCR1 Expression

Semnani

Mahapatra

Dembele

et al. 2010

The Journal of Immunology

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APC dysfunction has been postulated to mediate some of the parasite-specific T cell unresponsiveness seen in patent filarial infection. We have shown that live microfilariae of Brugia malayi induce caspase-dependent apoptosis in human monocyte-derived dendritic cells (DCs) in vitro. This study addresses whether apoptosis observed in vitro extends to patent filarial infections in humans and is reflected in the number of circulating myeloid DCs (mDCs; CD11c−CD123lo) in peripheral blood of infected microfilaremic individuals. Utilizing flow cytometry to identify DC subpopulations (mDCs and plasmacytoid DCs [pDCs]) based on expression of CD11c and CD123, we found a significant increase in numbers of circulating mDCs (CD11c+CD123lo) in filaria-infected individuals compared with uninfected controls from the same filaria-endemic region of Mali. Total numbers of pDCs, monocytes, and lymphocytes did not differ between the two groups. To investigate potential causes of differences in mDC numbers between the two groups, we assessed chemokine receptor expression on mDCs. Our data indicate that filaria-infected individuals had a lower percentage of circulating CCR1+ mDCs and a higher percentage of circulating CCR5+ mDCs and pDCs. Finally, live microfilariae of B. malayi were able to downregulate cell-surface expression of CCR1 on monocyte-derived DCs and diminish their calcium flux in response to stimulation by a CCR1 ligand. These findings suggest that microfilaria are capable of altering mDC migration through downregulation of expression of some chemokine receptors and their signaling functions. These observations have major implications for regulation of immune responses to these long-lived parasites.

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“…Expression of genes encoding other chemokines and chemokine receptors such as CCL2 (Monocyte Chemoattractant Protein‐1; MCP‐1), CCL4 (MIP‐1β), CCL7 (MCP‐3), CCL11 (Eotaxin‐1), CCL12 (MCP‐5), CCR1, CCR2, CCR3 and CCR4 have been shown to be induced in pulmonary models of schistosome induced granuloma formation (99–102) but the effect of these chemokines on granuloma formation and fibrosis is unknown. Together these findings suggest the balance of chemokine production and chemokine receptor activation is likely important in determining the fate of schistosome infection in animals and humans (103).…”

Section: Immunopathology Of Hepatic Schistosomiasismentioning

confidence: 93%

Immunopathogenesis of human schistosomiasis

Burke

Jones

Gobert

et al. 2009

Parasite Immunology

347

326

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Schistosomiasis continues to be a significant cause of parasitic morbidity and mortality worldwide. This review considers the basic features of the pathology and clinical outcomes of hepatointestinal and genitourinary schistosomiasis, presents an overview of the numerous studies on animal models that have clarified many of the immunopathological features, and provides insight into our current understanding of the immunopathogenesis and genetic control of human schistosomiasis. In murine schistosomiasis, pathology is induced by a CD4(+) Th2 driven granulomatous response directed against schistosome eggs lodged in the host liver. The Th2 cytokines IL-4 and IL-13 drive this response, whereas IL-10, IL13Ralpha2, IFN-gamma and a subset of regulatory T-cells act to limit schistosome induced pathology. A variety of cell types including hepatic stellate cells, alternatively activated macrophages and regulatory T-cells have also been implicated in the pathogenesis of schistosomiasis. Current knowledge suggests the immunopathogenic mechanisms underlying human schistosomiasis are likely to be similar. The review also considers the future development of anti-pathology schistosome vaccines. As fibrosis is an important feature of many other diseases such as Crohn's disease and sarcoidosis, a comprehensive understanding of the cellular and molecular mechanisms involved in schistosomiasis may also ultimately contribute to the development an effective disease intervention strategy for other granulofibrotic diseases.

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The role of chemokines in Schistosoma mansoni infection: insights from human disease and murine models

Abstract: Chemokines are a superfamily of low-molecular-weight

Cited by 12 publications

References 39 publications

Experimental Infection withSchistosoma mansoniin CCR5-Deficient Mice Is Associated with Increased Disease Severity, as CCR5 Plays a Role in Controlling Granulomatous Inflammation

Experimental Infection withSchistosoma mansoniin CCR5-Deficient Mice Is Associated with Increased Disease Severity, as CCR5 Plays a Role in Controlling Granulomatous Inflammation

Expanded Numbers of Circulating Myeloid Dendritic Cells in Patent Human Filarial Infection Reflect Lower CCR1 Expression

Immunopathogenesis of human schistosomiasis

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