Immune receptors and adhesion molecules in human pulmonary leptospirosis

Bernardi, Fabı́ola Del Carlo; Ctenas, Bruno; Silva, Luiz Fernando Ferraz da; Nicodemo, Antônio Carlos; Saldiva, Paulo Hilário Nascimento; Dolhnikoff, Marisa; Mauad, Thaís

doi:10.1016/j.humpath.2011.11.017

Cited by 28 publications

(24 citation statements)

References 30 publications

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“…Hence, we focused on TLR2 expression and showed that it was significantly up-regulated during leptospirosis. It has been found that TLR2 is upregulated on endothelial cells in lung samples of fatal leptospirosis [40]. TLR2 stimulation by LPS should induce CXCL8 synthesis and secretion at least in vitro [36] and yet this was not detected in our patients.…”

Section: Discussionmentioning

confidence: 71%

Major Neutrophilia Observed in Acute Phase of Human Leptospirosis Is Not Associated with Increased Expression of Granulocyte Cell Activation Markers

et al. 2016

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It has long been known that pathogenic Leptospira can mobilize the immune system but the specific contribution of neutrophils to control the infectious challenge remains to be clarified. We herein analyzed the phenotype of circulating neutrophils of patients with leptospirosis and healthy controls for the expression of toll-like receptor (TLR) type 2 (TLR2, to sense the leptospiral LPS) and several activation markers: interleukin 8 chemokine receptor CD182 (CXCR2), CD11b of the integrin/opsonin complement receptor type 3 (CR3) and CD15 (ligand of the selectin). The plasmatic level of the main CD182 ligand, interleukin 8 (CXCL8), was measured by ELISA. Hospitalized leptospirosis cases showed marked neutrophilia, particularly in the most severe cases. Interestingly, TLR2 was significantly increased in leptospirosis but identical levels of CD182 and CD11b were detected when compared to controls. CD15 was significantly decreased on neutrophils in leptospirosis but returned to normal within 1 month. Basal levels of IL-8 were measured in control subjects and were not increased in leptospirosis cases at the initial stage of the disease. In conclusion, we observed that neutrophils failed to regulate the expression of several of the receptors involved in cell activation and recruitment. This study further emphasizes the paradigm that neutrophils may be impaired in their overall capacity to thwart bacterial infection in leptospirosis patients.

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Section: Discussionmentioning

confidence: 71%

Major Neutrophilia Observed in Acute Phase of Human Leptospirosis Is Not Associated with Increased Expression of Granulocyte Cell Activation Markers

et al. 2016

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“…It may lead to a severe multiorgan failure (Morbus Weil, or Weil's disease) (7). In recent years, life-threatening and fatal cases have been due most often to pulmonary hemorrhages caused by vasculitis of small vessels (1,6,(8)(9)(10).…”

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confidence: 99%

Specific CD4⁺T-Cell Reactivity and Cytokine Release in Different Clinical Presentations of Leptospirosis

Volz

Moos

Allers

et al. 2015

Clin. Vaccine Immunol.

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dClinical manifestations of leptospirosis are highly variable: from asymptomatic to severe and potentially fatal. The outcome of the disease is usually determined in the immunological phase, beginning in the second week of symptoms. The underlying mechanisms, predictive factors, and individual immune responses that contribute to clinical variations are not well understood. The aim of this study was to determine the specifics of CD4 ؉ T-cell reactivity and cytokine release after stimulation with leptospiral antigens in patients with leptospirosis of different disease severities (patients with mild and severe symptoms) and in control subjects (with and without proven exposure to Leptospira). Whole-blood specimens were stimulated with Leptospira antigens in vitro. Subsequently, intracellular staining of cytokines was performed, and flow cytometry was used to assess the expression of CD40 ligand (CD40L) and the production of gamma interferon (IFN-␥), interleukin-10 (IL-10), IL-2, and tumor necrosis factor alpha (TNF-␣) by CD4 ؉ T cells. The production of inflammatory cytokines such as TNF-␣ by CD4 ؉ T cells after stimulation with leptospiral antigens was highest in patients with severe disease. In contrast, the ratio of IL-10 production to TNF-␣ production was higher in exposed subjects than in patients with mild and severe disease. Levels of proinflammatory cytokines such as TNF-␣ may be useful markers of the severity of the immunological phase of leptospirosis. IL-10 production by T cells after antigen-specific stimulation may indicate a more successful downregulation of the inflammatory response and may contribute to an asymptomatic course of the disease.

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“…The diagnosis was confirmed in nasopharyngeal swab specimens using a real-time reverse transcriptase polymerase chain reaction (rRT-PCR) test, in accordance with the guidelines from the Centers for Disease Control and Prevention (CDC) [15]. Leptospirosis diagnosis was clinically assessed and confirmed either by an at least 4-fold increase in the microagglutination titer, a single microagglutination titer greater than 1:400, and/or detection of leptospiral antigen in the biopsy or autopsy specimens [14, 18]. We described these cohorts in previous studies [15, 18–20].…”

Section: Methodsmentioning

confidence: 99%

“…Leptospirosis diagnosis was clinically assessed and confirmed either by an at least 4-fold increase in the microagglutination titer, a single microagglutination titer greater than 1:400, and/or detection of leptospiral antigen in the biopsy or autopsy specimens [14, 18]. We described these cohorts in previous studies [15, 18–20]. …”

Section: Methodsmentioning

confidence: 99%

The Expression of Water and Ion Channels in Diffuse Alveolar Damage Is Not Dependent on DAD Etiology

et al. 2016

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IntroductionAquaporins and ion channels are membrane proteins that facilitate the rapid movement of water and solutes across biological membranes. Experimental and in vitro studies reported that the function of these channels and pulmonary edema resolution are impaired in acute lung injury (ALI). Although current evidence indicates that alveolar fluid clearance is impaired in patients with ALI/diffuse alveolar damage (DAD), few human studies have addressed the alterations in pulmonary channels in this clinical condition. Additionally, it is not known whether the primary cause of DAD is a relevant variable for the channel dysfunction.MethodsAutopsied lungs of 43 patients with acute respiratory failure (ARF) due to DAD of three different etiologies, non-pulmonary sepsis, H1N1 viral infection and leptospirosis, were compared to 18 normal lungs. We quantified the expression of aquaporin (AQP) 1, AQP3, AQP5, epithelial Na+ channel (ENaC) and sodium potassium ATPase (Na-K-ATPase) in the alveolar septum using immunohistochemistry and image analysis.ResultsThe DAD group presented with increased expression of AQP3, AQP5 and Na-K-ATPase and decreased expression of ENaC compared to controls. However, there was no difference in protein expression within the DAD groups of different etiologies.ConclusionWater and ion channels are altered in patients with ARF due to DAD. The cause of DAD does not seem to influence the level of impairment of these channels.

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Immune receptors and adhesion molecules in human pulmonary leptospirosis

Cited by 28 publications

References 30 publications

Major Neutrophilia Observed in Acute Phase of Human Leptospirosis Is Not Associated with Increased Expression of Granulocyte Cell Activation Markers

Major Neutrophilia Observed in Acute Phase of Human Leptospirosis Is Not Associated with Increased Expression of Granulocyte Cell Activation Markers

Specific CD4⁺T-Cell Reactivity and Cytokine Release in Different Clinical Presentations of Leptospirosis

The Expression of Water and Ion Channels in Diffuse Alveolar Damage Is Not Dependent on DAD Etiology

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Immune receptors and adhesion molecules in human pulmonary leptospirosis

Cited by 28 publications

References 30 publications

Major Neutrophilia Observed in Acute Phase of Human Leptospirosis Is Not Associated with Increased Expression of Granulocyte Cell Activation Markers

Major Neutrophilia Observed in Acute Phase of Human Leptospirosis Is Not Associated with Increased Expression of Granulocyte Cell Activation Markers

Specific CD4+T-Cell Reactivity and Cytokine Release in Different Clinical Presentations of Leptospirosis

The Expression of Water and Ion Channels in Diffuse Alveolar Damage Is Not Dependent on DAD Etiology

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Specific CD4⁺T-Cell Reactivity and Cytokine Release in Different Clinical Presentations of Leptospirosis