Altered Toll-Like Receptor-4 Response to Lipopolysaccharides in Infants Exposed to HIV-1 and Its Preventive Therapy.

Anicet Christel Maloupazoa Siawaya,Ofilia Mvoundza Ndjindji,Chérone Nancy Mbani Mpega,Amandine Mveang-Nzoghe,Marielle Leboueny,Joel Fleury Djoba Siawaya,Armel Mintsa Ndong,Paulin N. Essone,Eliane Kuissi Kamgaing,Roselyne Kengue Boussougou

doi:10.3389/fimmu.2018.00222

Abstract

Pathogen sensing and recognition through pattern recognition receptors, and subsequent production of pro-inflammatory cytokines, is the cornerstone of the innate immune system. Despite the fact that HIV-exposed uninfected (HEU) infants are prone to serious bacterial infections, no study has focused on the functionality of their bacteria recognition system. This is the first study to investigate baseline levels of three critically important immune response molecules in this population: complement component (C)-3, toll-like receptor (TLR)-4, and C-reactive protein (CRP). We enrolled 16 HEU and 6 HIV-unexposed (HU) infants. TLR4 function was investigated by stimulating whole blood with increasing concentrations of TLR4-agonist ultrapure lipopolysaccharides. TLR4/TLR4-agonist dose response were assessed by measuring IL-6 secretion. Complement C3 and CRP were measured by photo spectrometry. Data showed no significant differences in baseline concentration of CRP between HEU and HU infants. Complement C3 was significantly higher in HEU infants than HU infants. TLR4 anergy was observed in 7 of 12 HEU infants, whereas the rest of HEU infants (n = 4) and the control HU infants tested (n = 3) showed responsive TLR4. None of the HEU infants investigated in this study had severe infections in the year after their birth. In conclusion, TLR4 anergy can occur in HEU infants without necessarily translating to increased vulnerability to infectious diseases.

Highlights

Progress in the prevention of mother-to-child transmission of HIV has led to a significant reduction of mother-to-child HIV transmission rate, increasing the population of HIV-exposed uninfected (HEU) infants [1,2,3]
Because of the critical role of these three molecules, we investigated the function of TLR4 and assessed the baseline levels of complement C3 and C-reactive protein (CRP) in HEU infants
To assess the baseline inflammatory status of infants (HEU: N = 11; HU: N = 6), we investigated the circulating levels of complement C3 and CRP

Summary

Introduction

Progress in the prevention of mother-to-child transmission of HIV has led to a significant reduction of mother-to-child HIV transmission rate, increasing the population of HIV-exposed uninfected (HEU) infants [1,2,3]. HEU infants are a growing population with over a million infants born every year from HIV-infected mothers [2]. Studies have shown that HEU infants are Impaired TLR-4 Function in HEU Infants more vulnerable to diseases than infants born from HIV free mothers [4,5,6,7,8]. The global efforts to understand HEU infants’ increased susceptibility to infections during the first months of their life has shed some light on the immune determinants of their susceptibility. Others have reported impaired humoral response [10, 11], altered chemokine receptor expression by CD4+ T cells [12], altered natural killer cell function, and reduced thymic output of naive CD4+ cells [13]

Methods

Results

Conclusion