B-cell activating factor deficiency suppresses splenomegaly during Leishmania donovani infection

Omachi, Satoko; Fujii, Wataru; Azuma, Natsuho; Morimoto, Ayako; Sanjoba, Chizu; Matsumoto, Yoshitsugu; Goto, Yasuyuki

doi:10.1016/j.bbrc.2017.06.005

Cited by 15 publications

(13 citation statements)

References 36 publications

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“…However, mechanisms for the enlargement of spleen and liver during experimental VL may be quite different and these organomegalies may occur as independent events. Firstly, splenomegaly during experimental VL is accompanied by an increase in cell numbers [30], whilst hepatomegaly is not -as demonstrated in the present study. Secondly, our previous studies using genetically modified mice demonstrated that deficiency in host molecules BAFF and MRP14 leads to attenuation of splenomegaly, but not hepatomegaly, in L. donovani infection [30,31].…”

Section: Discussionsupporting

confidence: 69%

“…Firstly, splenomegaly during experimental VL is accompanied by an increase in cell numbers [30], whilst hepatomegaly is not -as demonstrated in the present study. Secondly, our previous studies using genetically modified mice demonstrated that deficiency in host molecules BAFF and MRP14 leads to attenuation of splenomegaly, but not hepatomegaly, in L. donovani infection [30,31]. Although it is known that dysfunction or damage in the liver or the spleen often affects the other, the influence of L. donovani infection on these organs does not appear very closely connected.…”

Section: Discussionsupporting

confidence: 69%

“…One of the best known is sinusoidal obstruction; sinusoidal obstruction syndrome is caused by swelling and detachment of the sinusoidal endothelium, leading to hypercoagulability and obstruction of the sinusoids [33]. Aberrant production of immunoglobulins during experimental VL [30] implies that the coagulation system is hyper-activated in the infected mice and that the endothelium is damaged by inflammation. Contrary to this, however, there was no apparent thrombosis (Figure S3), nor was there any evidence of platelet extravasation and aggregation in the space of Disse (Figure S3), which would otherwise be an indicator of damage to the sinusoidal endothelium.…”

Section: Discussionmentioning

confidence: 99%

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Hepatomegaly Associated with Non-Obstructive Sinusoidal Dilation in Experimental Visceral Leishmaniasis

et al. 2021

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Visceral leishmaniasis (VL) is the most severe form of leishmaniasis caused by protozoan parasites of the genus Leishmania. Hepatomegaly is one of the most frequent clinical manifestations of VL, whereas immunopathology of the symptom has not been well investigated. Using our chronic model of experimental VL, we examined the influence of Leishmania donovani infection on the liver by clinical, histological, and biochemical analyses. The infected mice showed increased liver weight 24 weeks post-infection. Although an increase in serum ALT and inflammatory cell accumulation were observed in the livers of infected mice, no apparent parenchymal necrosis or fibrosis was observed. Tissue water content analyses demonstrated that increased liver weight was predominantly due to an increase in water weight. Together with the finding of hepatic sinusoidal dilation, these results suggested that edema associated with sinusoidal dilation causes hepatomegaly in L. donovani infection. Immunostaining of platelets and erythrocytes showed no thrombus formation or damage to the sinusoidal endothelium in the liver of infected mice. Taken together, these results suggest that hepatomegaly during experimental VL is caused by non-obstructive sinusoidal dilation.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

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Hepatomegaly Associated with Non-Obstructive Sinusoidal Dilation in Experimental Visceral Leishmaniasis

et al. 2021

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“…However, increased expression levels of BAFF and APRIL can also lead to dysregulated B cell responses and susceptibility to parasites. In visceral leishmaniasis, polyclonal B cell activation and hypergammaglobulinemia are associated with APRIL and BAFF expression in the spleens of infected dogs and in sera of infected mice, which may be responsible for the inefficient humoral immune response and disease progression seen in leishmaniasis (162,163). Similarly, in the chronic phase of Chagas' disease, hypergammaglobulinemia caused by excessive polyclonal B cell activation is recognized as the source of circulating autoantibodies (164), and BAFF secreted from myeloid cells seems to be responsible for polyclonal B cell activation (165) (Table 4 and Fig.…”

Section: Parasites Leishmaniasis and Chagas' Diseasementioning

confidence: 99%

The Role of BAFF System Molecules in Host Response to Pathogens

Sakai

Akkoyunlu

2017

Clin Microbiol Rev

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The two ligands B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) and the three receptors BAFF receptor (BAFF-R), transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI), and B cell maturation antigen (BCMA) are members of the "BAFF system molecules." BAFF system molecules are primarily involved in B cell homeostasis. The relevance of BAFF system molecules in host responses to microbial assaults has been investigated in clinical studies and in mice deficient for each of these molecules. Many microbial products modulate the expression of these molecules. Data from clinical studies suggest a correlation between increased expression levels of BAFF system molecules and elevated B cell responses. Depending on the pathogen, heightened B cell responses may strengthen the host response or promote susceptibility. Whereas pathogen-mediated increases in the expression levels of the ligands and/or the receptors appear to promote microbial clearance, certain pathogens have evolved to ablate B cell responses by suppressing the expression of TACI and/or BAFF-R on B cells. Other than its well-established role in B cell responses, the TACI-mediated activation of macrophages is also implicated in resistance to intracellular pathogens. An improved understanding of the role that BAFF system molecules play in infection may assist in devising novel strategies for vaccine development.

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“…In ZVL, an elevated amount plasma cells accumulates in the splenic RP [9]. At least two phenomena may contribute to spleen plasmacytosis in ZVL: (1) specific or polyclonal (not specific) B cell activation by Leishmania or coinfecting pathogens [10], and the homing and extended survival of otherwise short-lived plasma cell induced by BAFF, APRIL, and CXCL-12 [11,12]. Although the plasma cell density in the splenic RP correlates with the levels of hypergammaglobulinemia observed in ZVL, little is known about whether the fraction of the plasma cells present in spleen is committed with anti-Leishmania specific antibody production [13,14].…”

Section: Introductionmentioning

confidence: 99%

Anti-Leishmania infantum Antibody-Producing Plasma Cells in the Spleen in Canine Visceral Leishmaniasis

et al. 2021

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The spleen is involved in visceral leishmaniasis immunopathogenesis, and presents alterations in white-pulp microenvironments that are associated with an increased susceptibility to coinfections and patient death. Plasmacytosis in splenic red pulp (RP) is one observed alteration, but the specificity of antibody-secreting cells and the distribution of them has not yet been evaluated. We biotinylated soluble L. infantum membrane antigens (bSLMA) used as probes in modified immunohistochemistry, and detected the presence of anti-L. infantum antibody-secreting cells. Were used spleens from eight dogs from the endemic area for canine visceral leishmaniasis (CanL), and three healthier controls. The spleen sections were cryopreserved, and we performed modified immunohistochemistry. The ratio of plasma cells which were reactive to bSLMA (Anti-Leish-PC) in the spleen RP and periarteriolar lymphatic sheath (PALS) were calculated. Dogs with CanL present hyperglobulinemia and more plasma cells in their RP than the controls. Furthermore, dogs with CanL presented a lower proportion of Anti-Leish-PC in their RP than in PALS. Likewise, dysproteinemia was related to RP and PALS plasmacytosis, and a more severe clinical profile.

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B-cell activating factor deficiency suppresses splenomegaly during Leishmania donovani infection

Cited by 15 publications

References 36 publications

Hepatomegaly Associated with Non-Obstructive Sinusoidal Dilation in Experimental Visceral Leishmaniasis

Hepatomegaly Associated with Non-Obstructive Sinusoidal Dilation in Experimental Visceral Leishmaniasis

The Role of BAFF System Molecules in Host Response to Pathogens

Anti-Leishmania infantum Antibody-Producing Plasma Cells in the Spleen in Canine Visceral Leishmaniasis

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