CXCR4 and CCR5 receptor expression by CD4+ T cells and CD14+ Monocytes in paediatric Plasmodium Falciparum-HIV -1 Co-Infection within Western Kenya
| dc.contributor.author | Pande, James Raburn | |
| dc.date.accessioned | 2016-01-18T08:51:18Z | |
| dc.date.available | 2016-01-18T08:51:18Z | |
| dc.date.issued | 2015-03 | |
| dc.description | A research thesis submitted in partial fulfilment of the requirements for the award of the degree of Masters of Science (Immunology) in the School of Pure and Applied Sciences of Kenyatta University. March, 2015 | en_US |
| dc.description.abstract | HIV -1 and malaria pose the greatest health problem in holoendemic areas of malaria infection affecting about four million people world-wide, especially in sub-Saharan Africa. The molecular interactions involving the relative expression of CXCR4 and CCR5 receptors by CD 14+ monocytes and CD4+ T cells are important immune networks for mv and malaria interaction. However, very little have been performed to assess the molecular mechanism underlying these interactions in children from Western Kenya where both malaria and HfV-! infection are common. To determine the levels of expression of CXCR4 and CCR5 by CD3+CD4+ T cells and CD14+ monocytes, and their association with parasitological and haematological measures during paediatric P. falciparum-Hiv-Y exposure and co-infection within Western Kenya, the parameters were examined through flow cytometric analyses on cells collected from children (age, <5 years; n=72) from western Kenya categorized into the following five groups: P. falciparum negative and HIV -1 negative {mal[ -]-HIV- 1[-], n=13} as the healthy control; P. falciparum positive and HIV-l negative {mal[+]-HIV-l[-], n=30}; P. falciparumpositive and HIV-I exposed {mal[+]-HIV- 1[exp], n= I7}; P. falciparum negative and HIV -1 positive {mal]- ]-HIV -1 [+], n=5}; and P.falciparum positive and HIV-I positive {mal[+]-HIV-I[+], n=7}. Age differed significantly across the groups (P=0.OI6) with the Hlv-J-positive groups having older children relative to the other groups. Proportions of CD3+CXCR4+ and CD3+CD4+CCR5+ cell subsets did not differ significantly across the groups (P=0.082 and P=0.099, respectively). In addition, proportions ofCDI4+CCR5+ cells were comparable (P=0.065). Comparing mal[+]-HIV-l[+] to mal[+]-HIV-I[-], and mal[+]-HIV-l[+] to mal[-]-HlV-I[-] revealed that only CD14 cells increased significantly (P=O.OOI for both). Comparing mal[-]-HIV-I[+] to mal[+]-HIV-I[exp] showed a significant decrease for proportions of CCR5+CDI4+ (P=0.023), while comparison of mal[-]-HIV-I[+] to malj-j-Hlv-L]-] revealed that CCR5+CD14+ significantly decreased (P=0.017). Spearman rank correlation test in the combined population of malaria-infected children revealed that CD3+CCR5+ population was inversely correlated significantly with age (r =-0.620, P=O.O18); and positively the CD3+ (r =0.363, P=0.008) and inversely CD3+CXCR4+ (r =-0.711, P=0.021) populations were correlated significantly with intra-monocytic pigment (PCM), while CD 14 cells were positively correlated significantly with CD3+CXCR4+ (r =0.636, P=0.048), CD4+CCR5+ (r =0.875, P<O.OOOl) and inversely to CD4+ cells (r =-0.271, P=0.036). Further correlation analyses revealed that CDI4+CXCR4+ was highly inversely correlated with the proportion of PCM (%) (r =-0.403, P =0.003) and PCN (%) (r =-0.432, P=0.002). Thus, an increase of CDI4+ due to malaria-Hl V-I co infection may be influencing an increase of CCR5 and CXCR4 receptors which are being down regulated by both PCM and PCN. In conclusion, the results presented here suggest a dysregulation of CXCR4 and CCR5 receptors expression on CD4+ and CD 14+ cells in children co-infected with malaria and HIV -1, and that altered expression may be driven, at least in part, through acquisition of PfHz by both neutrophils and monocytes. In order to curb the ingestions of these malaria pigments, malaria diagnosis and treatment should be done promptly. The study shows that early treatment of malaria will reduce chances of exacerbation of HfV -1 disease progression. | en_US |
| dc.identifier.uri | http://ir-library.ku.ac.ke/handle/123456789/14063 | |
| dc.language.iso | en | en_US |
| dc.publisher | Kenyatta University | en_US |
| dc.title | CXCR4 and CCR5 receptor expression by CD4+ T cells and CD14+ Monocytes in paediatric Plasmodium Falciparum-HIV -1 Co-Infection within Western Kenya | en_US |
| dc.type | Thesis | en_US |
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