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

Abstract

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.

Cytokine response in human leptospirosis with different clinical outcomes: a systematic review

“…The full-texts of the remaining 43 articles were examined for suitability to the review criteria, and 25 were excluded. After the screening procedure, 18 articles were selected for the systematic review [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. Selected articles were published over 18 years from 2000 to 2018.…”

Decrease in antithrombin III and prothrombin serum levels contribute to coagulation disorders during leptospirosis

“…Indeed, the production of inflammatory cytokines such as TNF-a by CD4+ T-cells after stimulation with antigens of Leptospira was highest in patients with severe disease (Volz et al, 2015).…”

Pathogenic <i>Leptospira</i>: Advances in understanding the molecular pathogenesis and virulence

“…Additional studies described the mechanisms for the pathogen adaptation to thermal conditions (Eshghi et al, 2015a,b) and tolerance (Petrosova and Picardeau, 2014) outside the mammalian host. In addition, the inflammatory cascades that cause clinical disease (Gasque and Jaffar-Bandjee, 2015;Volz et al, 2015), virulence related proteins factors (King et al, 2014), bacteria-host interactions (Lo et al, 2009;Vieira et al, 2012;Siqueira et al, 2013;Fernandes et al, 2015), organization of the cytoskeletal and cellular in the host protein (Schuller et al, 2015) and defense mechanisms by the host (Werts, 2010) by pathogenic Leptospira have been described. Recent studies also identified leucine-rich repeat proteins that are known to be epitopes mediating antigen interaction (Nitipan et al, 2013), immune response factors in lipoproteins on the outer membrane of L. interrogans (Lin et al, 2010), ion transport mechanisms (Wu et al, 2004) and amino acid metabolism (Krajewska et al, 2016).…”