Papers by Girmay Desalegn
European journal of medical research, Mar 17, 2024
Background There is a widespread co-infection of HIV and Helicobacter pylori (H. pylori) globally... more Background There is a widespread co-infection of HIV and Helicobacter pylori (H. pylori) globally, particularly in developing countries, and it has been suggested that this co-infection may affect the course of HIV disease. However, the interplay between H. pylori infection and HIV disease progression is not fully elucidated. In this study, we investigated the effect of H. pylori co-infection on CD4 + T cell count and HIV viral load dynamics in HIV-positive individuals in a high co-endemic setting. Methods A comparative cross-sectional study was conducted among 288 HIV-positive and 175 HIV-negative individuals, both with and without H. pylori infection. Among HIV-positive participants, 195 were on antiretroviral therapy (ART) and 93 were ART-naïve. CD4 + T cell count and HIV-1 viral load were measured and compared between H. pyloriinfected and-uninfected individuals, taking into account different HIV and ART status. Result Our study demonstrated that individuals infected with H. pylori had a significantly higher CD4 + T cell count compared to uninfected controls among both HIV-negative and HIV-positive participants, regardless of ART therapy. Conversely, HIV/H. pylori co-infected participants had lower HIV-1 viral load than those without H. pylori infection. Linear regression analysis further confirmed a positive association between H. pylori infection, along with other clinical factors such as BMI, ART, and duration of therapy, with CD4 + T cell count while indicating an inverse relationship with HIV-1 viral load in HIV-positive patients. Additionally, factors such as khat chewing, age and WHO clinical stage of HIV were associated with reduced CD4 + T cell count and increased HIV-1 viral load. Conclusion Our study demonstrates that H. pylori co-infection was associated with higher CD4 + T cell count and lower HIV-1 viral load in HIV-positive patients, regardless of ART status. These findings show a positive effect of H. pylori co-infection on the dynamics of HIV-related immunological and virological parameters. Further studies are needed to elucidate the underlying mechanisms of the observed effects.
Infection and drug resistance, Feb 1, 2024
npj Vaccines, 2024
Diarrhea caused by Shigella has been associated with high morbidity and mortality in young childr... more Diarrhea caused by Shigella has been associated with high morbidity and mortality in young children worldwide. There are no licensed vaccines, and those clinically advanced have restricted coverage as they elicit serotype-specific immunity while disease is caused by multiple circulating serotypes. Our group had previously reported a close association between serum antibodies to the Shigella virulence factor VirG (or IcsA) and clinical protection in infected individuals. VirG is highly conserved among Shigella strains and appealing as a broad-spectrum vaccine candidate. In this study, we investigated the immunogenicity and protective capacity of VirG as a subunit vaccine in mice. The surface-exposed alpha (α) domain of VirG (VirGα) was produced as a recombinant protein. This region has almost identical immune reactivity to full-length VirG. Administered intramuscularly with alum, VirGα elicited robust immune responses and high protective efficacy against S. flexneri 2a and S. sonnei. Almost complete protection was afforded by VirGα given intranasally with the E. coli double mutant heat-labile toxin (dmLT). VirGα-specific antibodies recognized VirG expressed on live Shigella, and blocked Shigella adhesion and invasion to human colonic cells. These results show for the first time that VirGα is a promising cross-protective vaccine candidate to prevent Shigella infection.
mSphere, Jun 22, 2023
Diarrhea caused by Shigella species results in long-term disability and mortality globally, dispr... more Diarrhea caused by Shigella species results in long-term disability and mortality globally, disproportionally affecting younger children living in poor countries. Although it is treatable by antibiotics, the rapid and widespread emergence of resistant strains and the highly contagious nature of the disease compel the development of preventive tools.
Nature Communications, Jul 19, 2019
Bone marrow-derived circulating monocytes contribute to the replenishment and maintenance of the ... more Bone marrow-derived circulating monocytes contribute to the replenishment and maintenance of the intestinal macrophage population. Intestinal monocytes undergo contextdependent phenotypic and functional adaptations to either maintain local immune balance or support intestinal inflammation. Here we use monocyte adoptive transfer to dissect the dynamics of monocyte-to-macrophage differentiation in normal and inflamed small intestine. We find that during homeostasis CCR2 and β7-integrin mediate constitutive homing of monocytes to the gut. By contrast, intestinal inflammation increases monocyte recruitment via CCR2, but not β7-integrin. In the non-inflamed intestine, monocytes gradually differentiate to express genes typically associated with tolerogenic macrophage functions. Conversely, immediately upon entry into the inflamed intestine, monocytes adapt a different expression pattern in a partly Trem-1-dependent manner. Our observations suggest that inflammation fundamentally changes the kinetics and modalities of monocyte differentiation in tissues.
Applied Microbiology and Biotechnology, Dec 21, 2021
Shigella spp. invade the colonic epithelium and cause bacillary dysentery in humans. Individuals ... more Shigella spp. invade the colonic epithelium and cause bacillary dysentery in humans. Individuals living in areas that lack access to clean water and sanitation are the most affected. Even though infection can be treated with antibiotics, Shigella antimicrobial drug resistance complicates clinical management. Despite decades of effort, there are no licensed vaccines to prevent shigellosis. The highly conserved invasion plasmid antigens (Ipa), which are components of the Shigella type III secretion system, participate in bacterial epithelial cell invasion and have been pursued as vaccine targets. However, expression and purification of these proteins in conventional cell-based systems have been challenging due to solubility issues and extremely low recovery yields. These difficulties have impeded manufacturing and clinical advancement. In this study, we describe a new method to express Ipa proteins using the Xpress +TM cell-free protein synthesis (CFPS) platform. Both IpaB and the C-terminal domain of IpaH1.4 (IpaH-CTD) were efficiently produced with this technology at yields > 200 mg/L. Furthermore, the expression was linearly scaled in a bioreactor under controlled conditions, and proteins were successfully purified using multimode column chromatography to > 95% purity as determined by SDS-PAGE. Biophysical characterization of the cell-free synthetized IpaB and IpaH-CTD using SEC-MALS analysis showed well-defined oligomeric states of the proteins in solution. Functional analysis revealed similar immunoreactivity as compared to antigens purified from E. coli. These results demonstrate the efficiency of CFPS for Shigella protein production; the practicality and scalability of this method will facilitate production of antigens for Shigella vaccine development and immunological analysis. Key points • First report of Shigella IpaB and IpaH produced at high purity and yield using CFPS • CFPS-IpaB and IpaH perform similarly to E. coli-produced proteins in immunoassays • CFPS-IpaB and IpaH react with Shigella-specific human antibodies and are immunogenic in mice.
International Journal of Infectious Diseases, Dec 1, 2020
Objective: To investigate the effect of pregnancy and HIV infection on detection performances of ... more Objective: To investigate the effect of pregnancy and HIV infection on detection performances of Tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube (QFTGIT) for the diagnosis of LTBI among women living in high TB and HIV endemic setting. Method: A cross-sectional study was conducted among women with and without pregnancy and HIV infection. Three-hundred twenty women were enrolled in this study and were diagnosed by TST and QFTGIT for the detection of LTBI. Results: The overall prevalence of LTBI among the enrolled women were 55.6%, 46.3% and 51.1% as determined by TST, QFTGIT and concordant TST/QFTGIT results respectively. Our
<p>The relationship between the frequencies of IFN-γ secreting CBMCs (n = 40) in response t... more <p>The relationship between the frequencies of IFN-γ secreting CBMCs (n = 40) in response to ESAT-6/CFP-10 cocktail (A) and PPD (B) with the concentration of total IgE of cord blood plasma (n = 40).</p
Background A lower CD4 + T cell count and a higher viral load are associated with acquired immuno... more Background A lower CD4 + T cell count and a higher viral load are associated with acquired immunodeficiency syndrome (AIDS). The co-infection of Helicobacter pylori (H. pylori) in HIV-positive patients may affect immune parameters of HIV-related disease progression. The purpose of this study is to assess the effects of H. pylori co-infection on CD4 + T cell counts and HIV viral loads among HIV patients who are receiving ART (antiretroviral therapy) and HIV patients without ART Method A comparative cross-sectional study was conducted on 264 individuals from June to September 2020 in Mekelle city, Tigray, northern Ethiopia. A mixed sampling technique was used. H. pylori was detected using stool antigen test; CD4 + T cell count was performed by the BD FACSPrestoTM Cartridge test; and viral load was analyzed by COBAS® AmpliPrep/COBAS® TaqMan® HIV-1. The data was entered using EPi-data and analyzed using SPSS V.20 and graph pad prism software V.8. To assess the association, a one-way ANO...
<p>A line through the origen is fitted to indicate the deviation of points from the perfect... more <p>A line through the origen is fitted to indicate the deviation of points from the perfect (r = 1) correlation line.</p
<p>The frequency of IFN-γ (A) and IL-4 (B) secreting CBMCs (n = 40) in response to EAST-6/C... more <p>The frequency of IFN-γ (A) and IL-4 (B) secreting CBMCs (n = 40) in response to EAST-6/CFP-10 cocktail stimulation between helminth positive (n = 20) and negative (n = 20) study participants respectively.</p
<p><i>H<sup>+</sup>L<sup>+</sup> = helminth & LTBI positi... more <p><i>H<sup>+</sup>L<sup>+</sup> = helminth & LTBI positive and H<sup>−</sup>L<sup>+</sup> = helminth negative & LTBI positive.</i></p
Additional file 4: Figure S4. Association of IL-2 production and T cell proliferation in response... more Additional file 4: Figure S4. Association of IL-2 production and T cell proliferation in response to M. tuberculosis antigens. Correlation between frequency of IL-2-secreting cells and proliferating T cells among total PBMCs after stimulation with PPD (n = 9) and ESAT-6 (n = 10). Spearman correlation was used to calculate correlation coefficients (rs) and p values.
Additional file 3: Figure S3. CD4+ T cell count increased with therapy duration after HAART but n... more Additional file 3: Figure S3. CD4+ T cell count increased with therapy duration after HAART but not correlated with M. tuberculosis specific IL-2 nor IFN-γ responses. (a) CD4+ T cell count before and after HAART in HAART-treated participants (n = 23). p value was determined using Mann-Whitney test. (b) Correlation between the number of increased CD4+ T cells with HAART and duration of therapy. Correlation of the number of CD4+ T cells gained after therapy with PPD and ESAT-6 specific IL-2 (c) and IFN-γ (d) responses in HAART-treated participants (n = 23). Spearman correlation was used to calculate correlation coefficients (rs) and p values.
Additional file 2: Figure S2. Correlation of M. tuberculosis antigen-specific IL-2 responses and ... more Additional file 2: Figure S2. Correlation of M. tuberculosis antigen-specific IL-2 responses and CD4+ T cell count. Correlation between frequency IL-2 secreting cells responding to PPD or ESAT-6, and the CD4+ T cell count in HAART-naïve (a, n = 30) and HAART-treated (b, n = 31) participants. Spearman correlation was used to calculate correlation coefficients (rs) and p values.
Additional file 1: Figure S1. Correlation of M. tuberculosis antigen-specific IFN-γ responses and... more Additional file 1: Figure S1. Correlation of M. tuberculosis antigen-specific IFN-γ responses and CD4+ T cell count. Correlation between frequency IFN-γ secreting cells responding to PPD or ESAT-6, and the CD4+ T cell count in HAART-naïve (a, n = 30) and HAART-treated (b, n = 31) participants. Spearman correlation was used to calculate correlation coefficients (rs) and p values.
European Journal of Immunology, 2018
Clinical Immunology, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
BMC Immunology, 2019
BackgroundHIV-infected individuals with latent TB infection are at increased risk of developing a... more BackgroundHIV-infected individuals with latent TB infection are at increased risk of developing active TB. HAART greatly reduces the incidence rate of TB in HIV-infected patients and reconstitutesMycobacterium tuberculosis (M. tuberculosis)-specific immune response in the first 12 months of therapy. The durability of the anti-mycobacterial immune restoration after a year of HAART however remains less investigated.MethodA cross-sectional study was conducted to evaluateM. tuberculosis-specific functional immune responses in HIV/latent TB co-infected patients who were on HAART for at least 1.5 up to 9 years as compared to HAART-naïve patients. Three-hundred sixteen HIV-infected patients without active TB were screened by tuberculin skin testing forM. tuberculosisinfection and peripheral blood mononuclear cells (PBMCs) were isolated from 61 HIV/latent TB co-infected patients (30 HAART-naïve and 31 HAART-treated). IFN-γ and IL-2 ELISPOT as well as CFSE cell proliferation assays were perf...
PLoS ONE, 2014
Background: M. tuberculosis and helminth infection each affects one third of the world population... more Background: M. tuberculosis and helminth infection each affects one third of the world population. Helminth infections down regulate cell mediated immune responses and this may contribute to lower efficacy of BCG vaccination and higher prevalence of tuberculosis. Objective: To determine the effect of maternal helminth infection on maternal and neonatal immune function and immunity to TB. Methods: In this cross sectional study, eighty five pregnant women were screened for parasitic and latent TB infections using Kato-Katz and QFT-GIT tests, respectively. IFN-c and IL-4 ELISpot on Cord blood Mononuclear Cells, and total IgE and TB specific IgG ELISA on cord blood plasma was performed to investigate the possible effect of maternal helminth and/or latent TB co-infection on maternal and neonatal immune function and immunity to TB. Result: The prevalence of helminth infections in pregnant women was 27% (n = 23), with Schistosoma mansoni the most common helminth species observed (20% of women were infected). Among the total of 85 study participants 25.8% were QFT-GIT positive and 17% had an indeterminate result. The mean total IgE value of cord blood was significantly higher in helminth positive than negative women (0.76 vs 0.47, p = 0.042). Cross placental transfer of TB specific IgG was significantly higher in helminth positive (21.967.9) than negative (12.365.1), p = 0.002) Latent TB Infection positive participants. The IFNc response of CBMCs to ESAT-6/CFP-10 cocktail (50 vs 116, p = 0.018) and PPD (58 vs 123, p = 0.02) was significantly lower in helminth positive than negative participants. There was no significant difference in IL-4 response of CBMCs between helminth negative and positive participants. Conclusions: Maternal helminth infection had a significant association with the IFN-c response of CBMCs, total IgE and cross placental transfer of TB specific IgG. Therefore, further studies should be conducted to determine the effect of these factors on neonatal immune response to BCG vaccination.
Uploads
Papers by Girmay Desalegn