Altered thymocyte migration during experimental acute <i>Trypanosoma cruzi</i> infection: combined role of fibronectin and the chemokines CXCL12 and CCL4

Mendes-da-Cruz, Daniella Arêas; Silva, João; Cotta-de-Almeida, Vinı́cius; Savino, Wilson

doi:10.1002/eji.200535629

Cited by 52 publications

(67 citation statements)

References 30 publications

(34 reference statements)

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“…There have been reports that several chemokine ligands interact with the extracellular matrices and control cell migration (Pelletier et al 2000;Netelenbos et al 2002;Mendes-da-Cruz et al 2006), and that the extracellular matrices form chemokine gradients (Patel et al 2001). We suggest that an extracellular matrix causes the small-range chemotaxis of XCXCLC.…”

Section: Discussionmentioning

confidence: 52%

Chemokine ligand Xenopus CXCLC (XCXCLC) regulates cell movements during early morphogenesis

Goto¹,

Asashima²

2011

Development, Growth &Amp; Differentiation

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We cloned the gene for the CXC-type chemokine ligand, Xenopus CXCLC (XCXCLC), the transcripts of which were detected at the dorsal midline during the gastrula and neurula stages. XCXCLC overexpression resulted in the attraction of nearby mesodermal cells, and the excess of chemoattractant interfered with convergent and extension movements. The direction of the deep neural plate cells around the notoplate was also controlled by XCXCLC. Fluorescence signals for XCXCLC + enhanced green fluorescent protein derivatives accumulated around the notochord region. These results indicate that XCXCLC attracts adjacent cells to the midline region, so as to ensure accurate lateral-medial directional tissue convergence during gastrulation and neurulation.

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Section: Discussionmentioning

confidence: 52%

Chemokine ligand Xenopus CXCLC (XCXCLC) regulates cell movements during early morphogenesis

Goto¹,

Asashima²

2011

Development, Growth &Amp; Differentiation

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“…The importance of this signal pathway becomes apparent in studies with Trypanosoma cruzi, which is the causative agent of Chagas disease and also infects the thymus. In this study, the upregulation of CXCL12 in the thymus seems to lead to an outflow of immature T lymphocytes into the periphery (36). The surprising finding that highly pathogenic avian influenza A virus infection interferes with this important signal gave us reason to believe that the virus affects the thymus structure and function directly.…”

Section: Discussionmentioning

confidence: 62%

Highly Pathogenic Influenza Virus Infection of the Thymus Interferes with T Lymphocyte Development

Vogel

Haasbach

Reiling

et al. 2010

The Journal of Immunology

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Highly pathogenic avian influenza viruses (HPAIVs) cause severe disease in humans. Still, the basis for their increased pathogenesis remains unclear. Additionally, the high morbidity in the younger population stays inexplicable, and the recent pandemic H1N1v outbreak in 2009 demonstrated the urgent need for a better understanding about influenza virus infection. In the present study, we demonstrated that HPAIV infection of mice not only led to lung destruction but also to functional damage of the thymus. Moreover, respiratory dendritic cells in the lung functioned as targets for HPAIV infection being able to transport infectious virus from the lung into the thymus. The pandemic H1N1 influenza virus was able to infect respiratory dendritic cells without a proper transport to the thymus. The strong interference of HPAIV with the immune system is especially devastating for the host and can lead to lymphopenia. In summary, from our data, we conclude that highly pathogenic influenza viruses are able to reach the thymus via dendritic cells and to interfere with T lymphocyte development. Moreover, this exceptional mechanism might not only be found in influenza virus infection, but also might be the reason for the increased immune evasion of some new emerging pathogens.

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“…This was seen in both C57/BL6 and NOD thymocytes. Interestingly, it has also been reported in growth hormone transgenic mice, as well as in BALB/c mice infected with the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas' disease (16,17).…”

Section: Discussionmentioning

confidence: 90%

Multivectorial Abnormal Cell Migration in the NOD Mouse Thymus

Mendes-da-Cruz

Smaniotto

Keller

et al. 2008

The Journal of Immunology

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We previously described a fibronectin/VLA-5-dependent impairment of NOD thymocyte migration, correlated with partial thymocyte arrest within thymic perivascular spaces. Yet, NOD thymocytes still emigrate, suggesting the involvement of other cell migration-related alterations. In this context, the aim of this work was to study the role of extracellular matrix ligands, alone or in combination with the chemokine CXCL12, in NOD thymocyte migration. Intrathymic contents of CXCL12, fibronectin, and laminin were evaluated by immunohistochemistry while the expression of corresponding receptors was ascertained by flow cytometry. Thymocyte migration was measured using Transwell chambers and transendothelial migration was evaluated in the same system, but using an endothelial cell monolayer within the chambers. NOD thymocytes express much lower VLA-5 than C57BL/6 thymocytes. This defect was particularly severe in CD4+ thymocytes expressing Foxp3, thus in keeping with the arrest of Foxp3+ cells within the NOD giant perivascular spaces. We observed an enhancement in CXCL12, laminin, and fibronectin deposition and colocalization in the NOD thymus. Furthermore, we detected altered expression of the CXCL12 receptor CXCR4 and the laminin receptor VLA-6, as well as enhanced migratory capacity of NOD thymocytes toward these molecules, combined or alone. Moreover, transendothelial migration of NOD thymocytes was diminished in the presence of exogenous fibronectin. Our data unravel the existence of multiple cell migration-related abnormalities in NOD thymocytes, comprising both down- and up-regulation of specific responses. Although remaining to be experimentally demonstrated, these events may have consequences on the appearance of autoimmunity in NOD mice.

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Altered thymocyte migration during experimental acute Trypanosoma cruzi infection: combined role of fibronectin and the chemokines CXCL12 and CCL4

Cited by 52 publications

References 30 publications

Chemokine ligand Xenopus CXCLC (XCXCLC) regulates cell movements during early morphogenesis

Chemokine ligand Xenopus CXCLC (XCXCLC) regulates cell movements during early morphogenesis

Highly Pathogenic Influenza Virus Infection of the Thymus Interferes with T Lymphocyte Development

Multivectorial Abnormal Cell Migration in the NOD Mouse Thymus

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