A national field survey conducted from February to September 2019 helped us investigating the level of adherence among 1000 HIV+ pregnant women on antiretroviral therapy. We found that being a parent of an HIV+ child (P=0.001), or not sharing HIV status with spouse and/or family (P<0.001) were key determinants for the success of antiretroviral therapy. Some women found it difficult to socialise and spent more than they could afford on transport in order to obtain drugs as far away as possible for fear of being stigmatised if their status was discovered. Through a laboratory study, we characterized and compared the immune phenotypes between a native Cameroonian population(n=12) and a Caucasian group (n=14), in order to learn more about discrepancies that may be due to a distinct microbial environments lifetime and the immune response associated with this exposure built up over time, some intriguing difference was observed. While no difference was noted for the CD3+, CD4+ and CD8+ T cells population between the compared group, Africans appeared to have an expansion pool of central memory CD4+ T cells (p=0.01) compared to the Caucasian group with a major activated status of the CD4 compartment characterized by a higher exhibition of the CD69 marker (p=0.0001) knowing to be critical for the persistence of CD4+ T-cell memory in the bone marrow environment. Additionally, the functional activity of the CD4+ T cell among the African group were mainly dominated by –Th1– signature cytokines such as IFNγ, (p=0.00001) and TNFα (p=0.003). A proportion of CD4 perforin positive T cells were also found in the African group (p=0.006). However, no significant difference in maturation or activation of the CD8 compartment was observed between the two groups. Nevertheless, a proportion of CD8 CTLs i.e. CD8 perforin positive production was observed in the African group (p=0.0001). The latest raises many questions since cytokines environment such as IFN-γ from memory T cells is the most essential in instructing innate myeloid and lymphoid cell activation and differentiation into robust microbicidal effector cell. Furthermore, detailed descriptions of innate cell subsets with flow cytometry in our compared groups, mainly focused on NK cells, Monocytes and γδ T cells revealed significant divergent findings. We found a high frequency of classical monocytes (P=0.0001) in Africans compared to Caucasians, with a reduced population NK bright cells (P=0.005). This finding could widely influence the default developmental pathway of adaptive immune response inducted by these innate immune cells in case of infection by bacterial or viral pathogens. Our study focused on baseline characterization of immune phenotype, and it will be therefore interesting to assess functional capabilities within each subsets population between the compared group particularly among innate immune cell where striking difference was found and who could also exhibit trained immunity properties. In a century characterized by an apparent increase in emerging infectious diseases, knowledge of these fundamental subset differences have critical implications for public-health interventions and future research pathways aimed to strengthen the immune capacity of populations according to the sanitary mapping of pathogens living in their own environment.

Emerging and re-emerging infectious diseases: impact on social life and immune phenotype characterization in a cameroonian population

ZOGNING MAKEMJIO, EMELINE
2021

Abstract

A national field survey conducted from February to September 2019 helped us investigating the level of adherence among 1000 HIV+ pregnant women on antiretroviral therapy. We found that being a parent of an HIV+ child (P=0.001), or not sharing HIV status with spouse and/or family (P<0.001) were key determinants for the success of antiretroviral therapy. Some women found it difficult to socialise and spent more than they could afford on transport in order to obtain drugs as far away as possible for fear of being stigmatised if their status was discovered. Through a laboratory study, we characterized and compared the immune phenotypes between a native Cameroonian population(n=12) and a Caucasian group (n=14), in order to learn more about discrepancies that may be due to a distinct microbial environments lifetime and the immune response associated with this exposure built up over time, some intriguing difference was observed. While no difference was noted for the CD3+, CD4+ and CD8+ T cells population between the compared group, Africans appeared to have an expansion pool of central memory CD4+ T cells (p=0.01) compared to the Caucasian group with a major activated status of the CD4 compartment characterized by a higher exhibition of the CD69 marker (p=0.0001) knowing to be critical for the persistence of CD4+ T-cell memory in the bone marrow environment. Additionally, the functional activity of the CD4+ T cell among the African group were mainly dominated by –Th1– signature cytokines such as IFNγ, (p=0.00001) and TNFα (p=0.003). A proportion of CD4 perforin positive T cells were also found in the African group (p=0.006). However, no significant difference in maturation or activation of the CD8 compartment was observed between the two groups. Nevertheless, a proportion of CD8 CTLs i.e. CD8 perforin positive production was observed in the African group (p=0.0001). The latest raises many questions since cytokines environment such as IFN-γ from memory T cells is the most essential in instructing innate myeloid and lymphoid cell activation and differentiation into robust microbicidal effector cell. Furthermore, detailed descriptions of innate cell subsets with flow cytometry in our compared groups, mainly focused on NK cells, Monocytes and γδ T cells revealed significant divergent findings. We found a high frequency of classical monocytes (P=0.0001) in Africans compared to Caucasians, with a reduced population NK bright cells (P=0.005). This finding could widely influence the default developmental pathway of adaptive immune response inducted by these innate immune cells in case of infection by bacterial or viral pathogens. Our study focused on baseline characterization of immune phenotype, and it will be therefore interesting to assess functional capabilities within each subsets population between the compared group particularly among innate immune cell where striking difference was found and who could also exhibit trained immunity properties. In a century characterized by an apparent increase in emerging infectious diseases, knowledge of these fundamental subset differences have critical implications for public-health interventions and future research pathways aimed to strengthen the immune capacity of populations according to the sanitary mapping of pathogens living in their own environment.
2021
Inglese
MONTESANO, CARLA
Università degli Studi di Roma "Tor Vergata"
File in questo prodotto:
File Dimensione Formato  
PhD Thesis Emeline Zogning Makemjio.pdf

accesso solo da BNCF e BNCR

Dimensione 2.94 MB
Formato Adobe PDF
2.94 MB Adobe PDF

I documenti in UNITESI sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14242/300617
Il codice NBN di questa tesi è URN:NBN:IT:UNIROMA2-300617