Vittorio Colizzi

Influence of Pertussis toxin on CD1a Isoform Expression in Human Dendritic Cells

Pertussis toxin (PTX) is an exotoxin produced by Bordetella pertussis. It is known to exert adjuvant activities inducing Th1-launched immune responses. In this study, we show that PTX can selectively block the expression of CD1a isoform during the differentiation of human monocytes into dendritic cells. In fact, dendritic cells differentiated from monocytes in the presence of PTX do not express CD1a on their surface, unlike CD1b and CD1c isoforms, which are normally regulated. The impaired CD1a expression on cell membrane depends, at least partially, on decreased mRNA transcription and does not affect cellular capability to respond to other maturation stimuli. Since CD1a+ dendritic cells are involved in the early steps of primary immune response, the interference of PTX in the CD1a expression may be relevant for its employment as adjuvant.

Identification of a 35-kilodalton Mycobacterium tuberculosis protein containing B- and T-cell epitopes.

Screening of a Mycobacterium tuberculosis genomic DNA library in the lambda gt11 expression vector was carried out by using, as probes, sera from tuberculous patients and murine monoclonal antibody H61.3 recognizing a mycobacterial 35-kilodalton protein present only on the M. tuberculosis complex. The recombinant beta-galactosidase-fused protein present in the crude lysate induced the proliferation of T lymphocytes from patients with tuberculous pleuritis. As the recombinant insert contains an internal EcoRI restriction site, it was possible to identify two fragments, one proximal to the lacZ gene and 1.7 kilobases (kb) in size and the other distal to the lacZ gene and 2.2 kb in size. Southern blot analysis showed that both of them hybridized with the genomic DNA from M. tuberculosis and M. bovis but not with the DNA from other mycobacterial species. To perform extensive immunological studies, the amount of beta-galactosidase-fused protein being very low, we fused the 1.7-kb fragment to the N-terminal part of the gene coding for the DNA polymerase of bacteriophage MS2 in the expression vector pEx34. The fusion protein was partially purified, and subsequent Western blotting (immunoblotting) and T-cell proliferation experiments confirmed the presence of B- and T-cell mycobacterial epitopes. Furthermore, to isolate the chromosomal region containing the 35-kilodalton gene, we constructed another mycobacterial genomic library in the lambda 2001 vector by cloning 15 to 20 kb of foreign DNA. Screening of this library was carried out by using 1.7- and 2.2-kb recombinant fragments as probes. Restriction maps of some clones isolated were determined.

Increased autoreactive T cell frequency in tuberculous patients.

The development of putative self-MHC-reactive T cells and their precursor frequency was estimated in peripheral blood lymphocyte cultures stimulated in vitro with PPD. The role of foreign antigen in the generation of self-MHC-reactive T cells in vivo was analyzed by comparing the frequency of autoreactive T cells in the peripheral blood of tuberculous patients with that observed in healthy individuals. It was found that PPD in vitro and Mycobacterium tuberculosis infection in vivo increased substantially the generation of autoreactive T cells. Autoreactive T cell clones were shown (1) to recognize self MHC class II products; (2) to release gamma interferon in the absence of exogenous antigen, and (3) to express autocytotoxic activity. All these findings suggest that self-MHC-reactive T cells may be involved in the inflammatory response to M. tuberculosis.

Limiting dilution analysis of T cell unresponsiveness to mycobacteria in advanced disseminated tuberculosis

Peripheral blood mononuclear cells from patients with advanced disseminated tuberculosis (Dis-TB) do not respond to purified protein derivative (PPD) measured as cell proliferation, lymphokine production and interleukin (IL)-2 receptor (Tac antigen) expression. Limiting dilution analysis revealed “multi-hit” curves and low frequencies of PPD-reactive T cells in cultures of Dis-TB, and “single-hit” curves and high frequencies of PPD-reactive T cells in cultures of patients with localized form of pulmonary tuberculosis. Moreover, a strict relationship between Tac antigen expression and ability of exogenous IL-2 to enhance bulk culture cell proliferation was observed in Dis-TB patients.

Characterizing disability and perception of rehabilitation in the health District of Dschang, Cameroon

Aims: Disability and Rehabilitation Medicine are lagging behind in resource-limited settings (RLS). Baseline data from these settings should set goals for implementation. Following legislation (N°83/013/1983) on the protection of persons with disabilities in Cameroon, we sought to assess the types and potential determinants of physical disability, in order to set-up pitfalls towards better protection and promotion of human rights among disable Cameroonians. Methods: A cross-sectional study was conducted in June 2013 among physical disable individuals Calogero Foti1, Yannick N. Azeufack1,2, Martin S. Sobze2,3, Caterina Albensi1, Raoul W. Guetiya4,5, Rachel Mindjomo2, Michelle Sipewo2, Isabelle Djouana2, Axel Mba2, Elisabeth Metomo2, Ivan Nkone2, Mireille Ndongo2, Manjieli Awawou2, Charleine Tuiedjo2, James F. Onohiol2,3, Bruna Djeunang Dongho2,3, Patrick P. Nkamedjie2, Vittorio Colizzi4,6 Affiliations: 1Department of Clinical Sciences and Translational Medicine, Tor Vergata University, Rome, Italy; 2Department of Biomedical Sciences, Faculty of Sciences, University of Dschang, Cameroon; 3PIPAD Onlus, Dschang, Cameroon; 4Department of Biology, Faculty of Sciences, Tor Vergata University, Rome, Italy; 5Department of Biochemistry, Faculty of Sciences, University of Dschang, Cameroon; 6UNESCO Board of Multidisciplinary Biotechnology, Rome, Italy. Corresponding Author: Calogero Foti, MD, FEBPRM, Department of Clinical Sciences and Translational Medicine, Tor Vergata University, Rome; Italy; Via Montpellier, 1, Rome, Italy; 00133; E-mail: foti@med.uniroma2.it Received: 14 December 2015 Accepted: 31 March 2016 Published: 06 July 2016 living in the Health District of Dschang, a locality of the western region of Cameroon with people from diverse origins. A standard questionnaire identifying disabilities and related socio-economic and health determinants was administered to each identified disabled. Results: Out of 159 physically disabled (55.9% female and mean age 36 years [sd±17.26], 33.8% with primary educational-level), orthopedic (mainly due to fracture [45.8%] and infectious diseases [29.1%]) and neurological disabilities (mainly hemiplegia [33.3%], hemiparesis [23.8%], and monoplegia [23.8%]) were leading types of disabilities. Main causes of disability were traffic accidents (17.8%) and inappropriate medical interventions (14.5%). Disability onset decreased significantly with age (from 41.4% for 0–10 years to 0.6% for 70–80 years old, p=0.00508), and 50% experienced social discrimination/stigmatization. The disabled had low-income (XAF 50,000–200,000) to pay for rehabilitative care (XAF 10,000–100,000), and up to 83% appealed for an improved quality of rehabilitation medicine. Conclusion: Wider range of disabilities calls for safer transportation, medical interventions and disease prevention, implementing standard approaches towards rehabilitation and social reintegration of the disabled living in typical RLS.

Regulation of self-major histocompatibility complex reactive human T-cell clones

The proliferative response of human T-lymphocyte clones, (TLC) specific for self-major histocompatibility complex (MHC) products either alone or associated with PPD epitopes are inhibited in vitro by dexamethasone (DEX) and by a non-specific inhibitory factor(s) (nsINH) produced by PPD-activated T-cells. The inhibiting effect has been investigated by preincubating autoreactive and PPD-specific TLC with nsINH or DEX. Results obtained indicate that T-lymphocytes are the target of these two immunoregulatory molecules. Moreover, the addition of exogenous recombinant interleukin 2 (rIL-2) substantially reverses the inhibition observed in both nsINH- or DEX-treated cultures.

Why publishing the Journal of Public Health in Africa

The population of sub-Saharan Africa faces global health challenges more than any other part of the world, bearing the brunt of tuberculosis, malaria and HIV/AIDS. This region already carries 24% of the global disease burden and the situation is made worst by the advent of noncommunicable diseases, such as coronary heart disease, hypertension, cancer and diabetes (just to name a few). Thus the need for African scientists to disseminate research data in order to alleviate the continent’s huge disease burden and help the frail health systems affected by poverty, underdevelopment, conflicts and poorly managed government agencies. In our opinion, the Journal of Public Health in Africa responds to the need for a communication system aimed at reaching the widest audience of professionals worldwide in a shorter time than traditional publishing [...]

Youth awareness on sexually transmitted infections, HIV and AIDS in secondary schools in the Dschang Municipality (Cameroon): The mobile Caravan Project

Awareness is a preventive action to instill in individuals certain concepts to improve their health. It is an essential element in the prevention of sexually transmitted infection (STI)/HIV and early pregnancies among adolescents. In 2012, the prevalence of HIVin Cameroon was estimated at 4.3%. The young population appear to be the most affected (3.2%); very close to that of the Dschang Health District (Cameroon; 3.1%) in the 15-19 years age group. Theaimof this study was to evaluate the contribution of the Mobile Caravan project on the preventive aspect of STI/HIV/AIDS among youths of Dschang in 10 secondary schools within three years. 2029 students joined the project’s activities and 58.55% of them belonged to the age group of 16-21 years. Most students attended private schools. Nearly 3/4 of students (1515/2029) had an acceptable level of knowledge regarding STI/HIV/AIDS, which increased in number each year (from 641 to 716 students between 2012 and 2014). The Level of knowledge was significantly determinedby the study cycle (P=0.0004), the type of school (P=0.0027) and the year ofimplementation of activities (P=0.0026). The caravan project has greatly contributed to improving young peoples’ awareness on STI/HIV/AIDSin Dschang Municipality.