Mannose-binding lectin concentrations in people living with HIV/AIDS infected by HHV-8

Abstract

BackgroundMannose-binding lectin (MBL) plays an important role in the innate immune response by activating the complement system via the lectin pathway, and it has been studied in several viral infections; however, the influence of MBL in PLWHA infected with HHV-8 is unknown. The objective of this study was to verify the association of MBL deficient plasma concentrations in HIV/HHV-8 coinfected and HIV monoinfected patients and to correlate these concentrations with HIV viral load and CD4 counts in both groups.ResultsThis was an analytical study of case-controls consisting of PLWHA monitored at the medical outpatient of Infectious and Parasitic Diseases of the clinical hospital in the Federal University of Pernambuco. Plasma concentrations of MBL were obtained by an enzyme-linked immunosorbent assay (ELISA) using a commercial Human Mannose Binding Lectin kit (MyBioSource, Inc.) that was performed according to the manufacturer’s guidelines, with values < 100 ng/ml considered deficient. A total of 245 PLWHA samples were analysed; 118 were HIV/HHV-8 coinfected and 127 were HIV monoinfected; 5.1% (6/118) of the coinfected patients and 3.2% (4/127) of the monoinfected patients (p = 0.445) were considered plasma concentration deficient. The median of the plasma concentrations of MBL in the coinfected patients was 2803 log10 ng/ml and was 2.959 log10 ng/ml in the monoinfected patients (p = 0.001). There was an inverse correlation between the plasma concentrations of MBL and the HIV viral load in both groups, but no correlation with the CD4 count.ConclusionsAlthough the plasma concentrations considered deficient in MBL were not associated with HHV-8 infection in PLWHA, the coinfected patients showed lower MBL concentrations and an inverse correlation with HIV viral load, suggesting that there may be consumption and reduction of MBL due to opsonization of HIV and HHV-8, leading to the reduction of plasma MBL and non-accumulation in the circulation.

Early life imprints the hierarchy of T cell clone sizes

“…To determine a biologically plausible fluctuation strength , we analyzed the variability of clone sizes over time in a longitudinal repertoire sequencing study ( Chu et al, 2019 ). We first analyzed how much recently expanded clones contribute to the tail of the clone sizes, and found that only a small fraction of the largest clones in any sample were not already large at the earliest time point ( Figure 4A and Figure 4—figure supplement 1 ).…”

“…( C ) Fraction of clones with zero insertions as a function of age and clone size in a simulated cohort using a magnitude of clonal growth rate fluctuations inferred from the longitudinal data. Data source: Chu et al, 2019 .…”

“…To diminish the influence of sampling depth variations, we computationally subsampled all repertoires to an equal sample size of 5 · 10 5 counts. ( B,C ) Analysis of unsorted (TCR sequencing from all peripheral blood mononuclear cells), memory (CD3+, CD45+), and naive (CD3+, CD45RA+) blood samples from the same individual (Data source: Chu et al, 2019 ). ( B ) Clone size distributions in the different T cell compartments.…”

“…Here, we develop a theory of T cell dynamics throughout the human lifespan based on the statistical laws of repertoire organization and dynamics revealed by cohort and longitudinal human TCR repertoire sequencing ( Britanova et al, 2016 ; Emerson et al, 2017 ; Chu et al, 2019 ; Lindau et al, 2019 ). We find that clonal expansions during repertoire formation play an important role in establishing the clone size hierarchy, which is only slowly reshaped by fluctuating clonal selection during adult life.…”

PGC-1α regulates airway epithelial barrier dysfunction induced by house dust mite

“…Der p 1 is a cysteine protease allergen and is known to disrupt intracellular tight junction and promote the release of cytokines and alarmins such as TSLP, IL-33 and IL-25 by the protease activity during initial sensitization [ 62 , 63 ]. Der p 2 is known to mimic MD-2, which facilitates signaling through TLR4, leading to airway inflammation [ 64 ]. The current study expands previous findings and demonstrated a novel effect of Dermatophagoides pteronyssinus on airway epithelial cells.…”