Macrophage susceptibility to infection by Ghanaian Mycobacterium tuberculosis complex lineages 4 and 5 varies with self-reported ethnicity

BackgroundThe epidemiology of Mycobacterium tuberculosis complex (MTBC) lineage 5 (L5) infections in Ghana revealed a significantly increased prevalence in Ewes compared to other self-reported ethnic groups. In that context, we sought to investigate the early phase of tuberculosis (TB) infection using ex vivo infection of macrophages derived from the blood of Ewe and Akan ethnic group volunteers with MTBC L4 and L5 strains.MethodsThe study participants consisted of 16 controls, among which self-reported Akan and Ewe ethnicity was equally represented, as well as 20 cured TB cases consisting of 11 Akans and 9 Ewes. Peripheral blood mononuclear cells were isolated from both healthy controls and cured TB cases. CD14+ monocytes were isolated and differentiated into monocyte-derived macrophages (MDMs) before infection with L4 or L5 endemic strains. The bacterial load was assessed after 2 hours (uptake) as well as 3 and 7 days post-infection.ResultsWe observed a higher capacity of MDMs from Ewes to phagocytose L4 strains (p < 0.001), translating into a higher bacillary load on day 7 (p < 0.001) compared to L5, despite the higher replication rate of L5 in Ewe MDMs (fold change: 1.4 vs. 1.2, p = 0.03) among the controls. On the contrary, within macrophages from Akans, we observed a significantly higher phagocytic uptake of L5 (p < 0.001) compared to L4, also translating into a higher load on day 7 (p = 0.04). However, the replication rate of L4 in Akan MDMs was higher than that of L5 (fold change: L4 = 1.2, L4 = 1.1, p = 0.04). Although there was no significant difference in the uptake of L4 and L5 among cured TB cases, there was a higher bacterial load of both L4 (p = 0.02) and L5 (p = 0.02) on day 7 in Ewe MDMs.ConclusionOur results suggest that host ethnicity (driven by host genetic diversity), MTBC genetic diversity, and individual TB infection history are all acting together to modulate the outcome of macrophage infections by MTBC

Influence of α2-macroglobulin, anti-parasite IgM and ABO blood group on rosetting in <i>Plasmodium falciparum</i> clinical isolates and their associations with disease severity in a Ghanaian population

PURPOSE: The severity of Plasmodium falciparum infections is associated with the ability of the infected red blood cells to cytoadhere to host vascular endothelial surfaces and to uninfected RBCs. Host blood group antigens and two serum proteins α(2)-macroglobulin (α(2)M) and IgM have been implicated in rosette formation in laboratory-adapted P. falciparum. However, there is only limited information about these phenotypes in clinical isolates. METHODS: This was a hospital-based study involving children under 12 years-of-age reporting to the Hohoe Municipal Hospital with different clinical presentations of malaria. Parasite isolates were grown and rosette capabilities and characteristics were investigated by fluorescence microscopy. α(2)M and IgM were detected by ELISA. RESULTS: Rosette formation was observed in 46.8% (75/160) of the parasite isolates from all the blood groups tested. Rosettes were more prevalent (55%) among isolates from patients with severe malaria compared to isolates from patients with uncomplicated malaria (45%). Rosette prevalence was highest (30%) among patients with blood group O (30%) and B (29%), while the mean rosette frequency was higher in isolates from patients with blood group A (28.7). Rosette formation correlated negatively with age (r = −0.09, P= 0.008). Participants with severe malaria had a lower IgM concentration (3.683±3.553) than those with uncomplicated malaria (5.256±4.294) and the difference was significant (P= 0.0228). The mean concentrations of anti-parasite IgM measured among the clinical isolates which formed rosettes was lower (4.2 ±3.930 mg/mL), than that in the non rosetting clinical isolates (4.604 ±4.159 mg/mL) but the difference was not significant (P=0.2733). There was no significant difference in plasma α(2)M concentration between rosetting and non rosetting isolates (P=0.442). CONCLUSION: P. falciparum parasite rosette formation was affected by blood group type and plasma concentration of IgM. A lower IgM concentration was associated with severe malaria whilst a higher α(2)M concentration was associated with uncomplicated malaria