Targeting CD166+ lung cancer stem cells: Molecular study using murine dendritic cell vaccine.

PURPOSE: Cancer stem cells (CSC) are the most common causes of lung cancer relapse and mouse resistance to chemotherapy. CD166 was identified as CSC marker for lung cancer. Our study aimed to detect the effect of dendritic cell vaccine loaded with tumor cell lysate (TCL-DCV) on percentage of CD166+ CSC in lung of mice exposed to Benzo(a)Pyrene (BP). METHODS: Female albino mice were divided into 5 groups (22 mice per group): normal control (NC), lung cancer control (LCC) (50 mg/kg BP orally, twice weekly for four weeks), dendritic cell (DC), TCL-DCV and cisplatin. Cisplatin (6 mg/kg, intraperitoneal) was given in two doses (18th and 20th week). 1 × 106 cells of each of DC and TCL-DCV was given subcutaneously as cisplatin. At the end of experiment (22 weeks), lung tissue was used for evaluation of cytotoxic T lymphocyte antigen-4 (Ctla-4), transforming growth factor-ß (Tgf-ß), forkhead box protein P3 (Foxp3), programmed death ligand 1 (Pd-l1) and interleukin 12 (Il-12) gene expression using quantitative RT-PCR. The percentage of CD83+, CD8+ and CD166+ cells in lung tissue were measured using flow cytometry. RESULTS: The results revealed that TCL-DCV reversed the tumorigenic effect of BP in the lung as evidenced by histopathological examination. Compared to cisplatin, dendritic cell vaccination (TCL-DCV) significantly decreased percentage of CD166+ CSC. This anticancer stemness effect was attributed to the immune-stimulatory effect as indicated by increased percentage of CD83+ and CD8+ cells, upregulation of Il-12, and downregulation of Tgf-ß, Ctla-4, Pd-l1 and Foxp3 gene expression compared to LCC group. CONCLUSIONS: TCL-DCV ameliorated cancer stemness through modulating tumor immune archetypes which make it a potent therapeutic alternative to chemotherapy resistant cases.

Dual-targeted therapeutic strategy combining CSC-DC-based vaccine and cisplatin overcomes chemo-resistance in experimental mice model.

BACKGROUND AND PURPOSE: Emerging evidence suggests that one of the main reasons of chemotherapy treatment failure is the development of multi-drug resistance (MDR) associated with cancer stem cells (CSCs). Our aim is to identify a therapeutic strategy based on MDR-reversing agents. MATERIALS AND METHODS: CSC-enriched Ehrlich carcinoma (EC) cell cultures were prepared by drug-resistant selection method using different concentrations of cisplatin (CIS). Cell cultures following drug exposure were analyzed by flow cytometry for CSC surface markers CD44+/CD24-. We isolated murine bone marrow-derived dendritic cells (DCs) and then used them to prepare CSC-DC vaccine by pulsation with CSC-enriched lysate. DCs were examined by flow cytometry for phenotypic markers. Solid Ehrlich carcinoma bearing mice were injected with the CSC-DC vaccine in conjunction with repeated low doses of CIS. Tumor growth inhibition was evaluated and tumor tissues were excised and analyzed by real-time PCR to determine the relative gene expression levels of MDR and Bcl-2. Histopathological features of tumor tissues excised were examined. RESULTS AND CONCLUSION: Co-treatment with CSC-DC and CIS resulted in a significant tumor growth inhibition. Furthermore, the greatest response of downregulation of MDR and Bcl-2 relative gene expression were achieved in the same group. In parallel, the histopathological observations demonstrated enhanced apoptosis and absence of mitotic figures in tumor tissues of the co-treatment group. Dual targeting of resistant cancer cells using CSC-DC vaccine along with cisplatin represents a promising therapeutic strategy that could suppress tumor growth, circumvent MDR, and increase the efficacy of conventional chemotherapies.

Does the mosquito Culex pipiens represent a potential vector of hepatitis C virus?

Infection with hepatitis C virus (HCV) is a public health burden in several countries. Although transmission through blood is the most likely potential route of HCV infection, other sources warrant exploration. This study was designed to examine the possibility that the mosquito Culex pipiens (Diptera: Culicidae) might serve as a vector of HCV. A series of laboratory experiments were conducted in female Cx. pipiens that were fed on blood taken from HCV patients and tested for the presence of HCV RNAs using a reverse transcription polymerase chain reaction technique. In addition, the ability of the female mosquito to transmit HCV to human blood through membrane feeding or to its offspring (larvae) was tested. Although positive strand RNA was detected on days 1,7 and 14, negative strand HCV RNA was detected in mosquito body homogenate on days 7 and 14. Positive strands were also detected in the head, alimentary canal and salivary glands of mosquito adults at 1 week post-feeding, as well as in their offspring (larvae). An ex vivo assay demonstrated that HCV-infected mosquitoes were able to transmit the virus RNA into naive human blood samples via a membrane feeder. The present data indicate that the mosquito Cx. pipiens may be a potential vector of HCV.

[Sensitivity to antibiotics uropathogens bacteria in Nouakchott - Mauritania]. / La sensibilité aux antibiotiques des bactéries uropathogènes dans la ville de Nouakchott - Mauritanie.

INTRODUCTION: A urinary tract infection (UTI) is a frequent pathology in outpatients and admitted patients as well. In recent years, there has been an increase in the resistance of germs responsible for UTI to tested antibiotics, particularly because of the emergence of Enterobacteria secreting extended-spectrum beta-lactamase (ESBL). OBJECTIVE: The aim of this work was to study the epidemiology of germs responsible for urinary tract infections and their antibiotic sensitivity at three clinical laboratories in the city of Nouakchott (Mauritania) in all patients presenting to these laboratories for urine culture during a period of six months. METHODS: This is a prospective study conducted at three clinical laboratories in Nouakchott, over a period of six months from January 1st to June 30th 2014 for all patients coming to these laboratories for urinalysis test during this period. The culture was performed according to the usual techniques, and the antibiogram was done according to the recommendations of the Antibiogram Committee of the French Society of Microbiology. The statistical analysis was performed using SPSS Statistics 20. RESULTS: From 3082 urine exam, 568 were positive, which means 18.4%. These infections were for hospitalized patients (17.8%) and outpatients in particular (82.2%). Sex ratio F/M was 1.6. The epidemiology of urinary tract infections in these three medical analysis laboratories is comparable to the past studies data regarding age, sex, and the bacteria, the most frequently responsible (Escherichia coli 64.4%). But differences in the resistance of E. coli are observed: higher resistance to beta-lactam antibiotics, the quinolones, the fluoroquinolones, and cotrimoxazol. UTI was common in patients with urinary catheter (64.9%), diabetics (52.4%), hospitalized patients (49.3%) and pregnant women (38.7%). The prevalence of urinary tract infections caused by Enterobacteria ESBL in our study was 12.8%, of all urinary tract infections caused by Enterobacteria; 10.4 and 20.4% of the E. coli and Klebsiella spp, respectively produced a ESBL. CONCLUSION: The distribution of germs in our study is comparable to the literature, however, antibiotic resistance is higher in our study, which is probably a result of the inappropriate use of these drugs in our country, therefore it is important for us to create a good strategy to supply and distribute these drugs, as well as the review of the empirical treatment of UTI in our country. LEVEL OF EVIDENCE: 4.

IL-12 conditioning improves retrovirally mediated transduction efficiency of CD8+ T cells.

The ability to genetically modify T cells is a critical component to many immunotherapeutic strategies and research studies. However, the success of these approaches is often limited by transduction efficiency. As retroviral vectors require cell division for integration, transduction efficiency is dependent on the appropriate activation and culture conditions for T cells. Naive CD8(+) T cells, which are quiescent, must be first activated to induce cell division to allow genetic modification. To optimize this process, we activated mouse T cells with a panel of different cytokines, including interleukin-2 (IL-2), IL-4, IL-6, IL-7, IL-12, IL-15 and IL-23, known to act on T cells. After activation, cytokines were removed, and activated T cells were retrovirally transduced. We found that IL-12 preconditioning of mouse T cells greatly enhanced transduction efficiency, while preserving function and expansion potential. We also observed a similar transduction-enhancing effect of IL-12 preconditioning on human T cells. These findings provide a simple method to improve the transduction efficiencies of CD8(+) T cells.

In vitro and in vivo studies of the immunomodulatory effect of Echinacea purpurea on dendritic cells.

BACKGROUND: Extracts of Echinacea have been used traditionally for the treatment of diverse types of infections and wounds. They have become very familiar immunostimulant herbal medicine. However, the specific immunomodulatory effect of Echinacea remains to be elucidated. AIM: In our study, the effect of Echinacea purpurea extract on the generation of immature DCs from monocytes was described, as well as its effect on DC differentiation. In addition, an in vivo experiment was conducted to investigate whether treatment of mice with extracts derived from E. purpurea has immunomodulatory effect on murine splenic DCs. METHODS: Immature DCs were generated by incubating peripheral blood monocytes with cytokine cocktail (GM-CSF + IL-4) and matured by tumor necrosis factor-α (TNF-α). The cells were randomized to 5 groups to investigate E. purpurea effect in different stages. Phenotypic analysis of cell marker CD83-expressed on DCs was performed by flow cytometry. Mice were randomly divided into 3 groups; control, E. purpurea treated and E. purpurea-TNF-α treated group. The murine splenic DCs were isolated and phenotyped for CD83 and CD11c by flow cytometry. RESULTS: Treatment of monocytes with E. purpurea prior to addition of the maturation factor TNF-α resulted in a significant decrease in the yield of DC expressing CD83. On the other hand, immature DCs generated in the culture in the presence of GM-CSF and IL-4, when treated simultaneously with E. purpurea and TNF-α, exhibited an insignificant change in the yield of CD83-expressing DCs compared with untreated control. The in vivo experiments showed that splenic DCs obtained from mice treated with E. purpurea with or without TNF-α did not exhibit significant changes in CD83 or CD11c compared with those obtained from control mice. CONCLUSION: Our findings suggest that the immunomodulatory mechanisms of E. purpurea impact generation fate of DCs rather than differentiation stages. The results obtained in the in vivo study utilizing murine splenic DCs supported those observed in vitro.

Thymoquinone, the active ingredient of Nigella sativa seeds, enhances survival and activity of antigen-specific CD8-positive T cells in vitro.

Recent preclinical and clinical studies provide evidence that adoptive transfer of in vitro activated T cells can results in significant antitumour responses in vivo upon acquisition of certain survival and homing properties during in vitro activation. Based on recent studies showing in vivo antioxidant effects of thymoquinone (TQ), the active ingredient of Nigella sativa seeds, this study aims to determine whether or not TQ can increase survival and sustain the expression of the homing receptor CD62L in antigen-specific T cells in vitro. The results showed that stimulation of OT-1 (transgenic CD+) T cells with OVA antigen resulted in activation, as shown by a decrease in the surface expression of CD62L which coincided with significant apoptosis measured three and five days after antigen stimulation. Addition of low concentrations of TQ during CD85+ T-cell activation resulted in enhanced survival of the activated T cells and sustained expression of CD62L. These effects coincided with enhancement in the capability of CD8+ T cells to produce the effector cytokine interferon-gamma (IFNgamma). These results suggest that TQ has a beneficial effect in conditioning T cells in vitro for adoptive T-cell therapy against cancer and infectious disease.

The use of growth factors to modulate the activities of antigen-specific CD8+ T cells in vitro.

RATIONALE: Adoptive T cell therapy depends on the harvesting of the cells from the host, their activation in vitro, and their infusion back to the same host. The way of activating the T cells in vitro is a critical factor for their homing, survival and function in vivo. Sustaining T cell homing molecules, particularly CD62L, is benefic for the trafficking of the adoptive transferred cells. OBJECTIVE: The aim of the present study is to test whether insulin-like growth factor-1 (IGF-1), thymosin- α1 (T-α1) as well as all-trans retinoid acid (ATRA) alone or in combination with IL-2, IL-12, IL-15 can enhance the activation and survival phenotypes of antigen-activated T cells in vitro. METHODS & RESULTS: To this end, OT-1 transgenic T cells were used as a model. These CD8+ T cells recognize OVA peptide presented by MHC class-I. The results showed that antigen stimulation of OT1 cells resulted in their activation as evidenced by the decrease in surface expression of CD62L, analyzed for 3 days after antigen stimulation and was more pronounced on day 5. The addition of IL-12 or IGF-1 alone but not of IL-2, IL-15 augmented OT-1 cell activation measured on day 5. Interestingly, the combination of IL-12 with IGF-1 sustained the expression of CD62L on OT1 cells. Although the addition of ATRA alone or in combination with IL-12 resulted in decreases in CD62L expression on day 3, they showed a dose-dependent effect on the restoration of CD62L expression on day 5. The analysis of the activation-induced cell death (apoptosis) of OT1 cells showed an increased rate of death on day 5 than on day 3-post antigen stimulation. The addition of only IL-12 or IGF-1 alone, but not of IL-2, IL-15 or T- α1, decreased OT1 cell apoptosis on day 3. These anti-apoptotic effects of IL-12 and IGF- 1, however, were recovered on day 5-post stimulation. DISCUSSION: In conclusion, these results indicate that the activation phenotype and the survival of antigen-specific T cells can be differently modulated by immunomodulatory factors, where, interleukin-12 and IGF-1 induced the favorable effect. These results have a significant implication for T cell adoptive immunotherapy in different settings.

Protective effects of Nigella sativa oil and thymoquinone against toxicity induced by the anticancer drug cyclophosphamide.

Constituents of the Nigella sativa seed are reported to possess potent antioxidant effects. Treatment with anticancer drugs such as cyclophosphamide (CTX) is associated with significant toxicity due to over-production of reactive oxygen species, resulting in increased levels of oxidative stress. The aim of this study is to test whether or not N. sativa L oil (NSO) or its active ingredient, thymoquinone (TQ), can reduce CTX-induced toxicity. Male albino rats were treated with intraperitoneal administration of phosphate buffered saline (PBS) or 200 mg/Kg CTX followed by intragastric administration of NSO or TQ on alternate days for 12 days. Administration of NSO and TQ was initiated 6 h before or after CTX injection. Twenty-four hours after the last NSO and TQ treatment, blood and liver were harvested to analyse toxicity-related parameters. Treatment with CTX induced significant toxicity as shown by decrease in haemoglobin concentration and increases in blood sugar levels, activities of liver enzymes, bilirubin, urea, creatinine, lipids (triglyceride, cholesterol and low-density lipoprotein (LDL)-cholesterol) and lipid peroxidation in the liver. Treatment with NSO or TQ induced significant reduction in overall toxicity. The antitoxic effects of NSO and TQ were associated with induction of antioxidant mechanisms. These results suggest that administration of NSO or TQ can lower CTX-induced toxicity as shown by an up-regulation of antioxidant mechanisms, indicating a potential clinical application for these agents to minimise the toxic effects of treatment with anticancer drugs.

Loss of T cell-mediated antitumor immunity after construct-specific downregulation of retrovirally encoded T-cell receptor expression in vivo.

Adoptive T-cell therapy is clinically efficacious in the treatment of select cancers. However, it is often difficult to obtain adequate numbers of tumor-specific T cells for therapy. One method for overcoming this limitation is to generate tumor-specific T cells by retrovirally mediated T-cell-receptor (TCR) gene transfer. However, despite instances of therapeutic success, major obstacles remain, including attaining the survival of retrovirally modified T cells in vivo as well as inducing long-term and multi-gene retroviral expression. Using a murine model of adoptively transferred retrovirally modified CD8(+) T cells, where antitumor immunity was dependent on sustained, multigene expression, we found that in vitro assays are poor indicators of in vivo efficacy. Despite persisting for over 9 months in a nonlymphopenic environment, genetically modified T cells exhibited discordant retrovirally mediated gene expression in vivo not readily evident from initial in vitro assays. In particular, one of the two TCR subunit genes necessary for antigen specificity was selectively lost in vivo. As this discordant gene expression was associated with the loss of antitumor immunity, consideration of these findings may provide guidance in the design, evaluation and application of retroviral vectors for use in the treatment of cancer and other human disease.

N-3 polyunsaturated fatty acids accentuate B16 melanoma growth and metastasis through suppression of tumoricidal function of T cells and macrophages.

BACKGROUND: The antitumor effects of the n-3 polyunsaturated fatty acids (PUFAs) are still controversial and as yet undefined. MATERIALS AND METHODS: EPA-28, a fish oil enriched with n-3 PUFAs including eicosapentaenoic and docosahexaenoic acids, was administered subcutaneously into C57BL/6 mice before and after subcutaneous inoculation of B16 melanoma cells. The effects of EPA-28 on the antitumor activities of T cells and macrophages were investigated. RESULTS: The treatment of the mice with EPA-28 before and after the tumor inoculation enhanced the growth and metastasis of B16 melanoma and decreased the survival rate of the tumor-bearing mice. The treatment also decreased the number of CD4+ T cells in the spleen and tumor draining lymph nodes on day 14 after the tumor inoculation. Moreover, EPA-28 suppressed the antimelanoma cytolytic activity of T cells and macrophages of the tumor-bearing mice. CONCLUSION: The results suggest that EPA-28 treatment increased both the growth and metastasis of B16 melanoma cells by suppressing the cytolytic function of both T cells and macrophages.

In vivo acute depletion of CD8(+) T cells before murine cytomegalovirus infection upregulated innate antiviral activity of natural killer cells.

In this study, we investigated the effect of depletion of CD8(+) T cells on the activity of natural killer (NK) cells at an early phase of murine cytomegalovirus (MCMV) infection. For CD8(+) T cell depletion, mice were intraperitoneally treated with anti-CD8 mAb, purified from 2.43 hybridoma, for 2 consecutive days before or after infection. Three days after infection, we found that an acute depletion of CD8(+) T cells before infection caused a significant decrease in the viral load in liver and spleen. This effect coincided with an increase in numbers of CD3(-) NK1.1(+) cells in spleen and their expression of the early activation molecule CD69. Although cytolytic activity of NK cells increased on day 3 of infection in CD8-depleted mice, the level of IFN-gamma decreased in serum and supernatant of cultured spleen cells. In contrast to the effect of acute depletion of CD8(+) T cells before infection, the depletion after infection had no effect on the viral load or number and cytolytic function of NK cells. Lack of effects of CD8(+) T cell depletion on the viral load and NK cytolytic activity is also observed in CD8(+) knockout mice. In conclusion, the results suggest that an acute depletion of CD8(+) T cells before MCMV infection effectively upregulated the antiviral activity of NK cells. This effect appears to be mediated through an increase in numbers, activation and cytolytic activity of NK cells.

Protective effect of black seed oil from Nigella sativa against murine cytomegalovirus infection.

In this study, antiviral effect of black seed oil (BSO) from Nigella sativa was investigated using murine cytomegalovirus (MCMV) as a model. The viral load and innate immunity mediated by NK cells and Mφ during early stage of the infection were analyzed. Intraperitoneal (i.p.) administration of BSO to BALB/c mice, a susceptible strain of MCMV infection, strikingly inhibited the virus titers in spleen and liver on day 3 of infection with 1x10(5) PFU MCMV. This effect coincided with an increase in serum level of IFN-gamma. Although BSO treatment decreased both number and cytolytic function of NK cells on day 3 of infection, it increased numbers of Mφ and CD4(+) T cells. On day 10 of infection, the virus titer was undetectable in spleen and liver of BSO-treated mice, while it was detectable in control mice. Although spleen of both control and BSO-treated mice showed similar CTL activities on day 10 after infection, serum level of IFN-gamma in BSO-treated mice was higher. Furthermore, BSO treatment upregulated suppressor function of Mφ in spleen. These results show that BSO exhibited a striking antiviral effect against MCMV infection which may be mediated by increasing of Mφ number and function, and IFN-gamma production.

Mediation of the immunomodulatory effect of beta-estradiol on inflammatory responses by inhibition of recruitment and activation of inflammatory cells and their gene expression of TNF-alpha and IFN-gamma.

BACKGROUND: Estrogen has long been reported to show immunomodulatory effects on immune responses, yet, its specific anti-inflammatory mechanism is not clear. METHODS: In this study, we analyzed the effects of beta-estradiol (E2), at its contraceptive dose, on both T cell-independent and T cell-dependent inflammations, and the associated immune mechanism, in female mice. The T cell-independent inflammation was locally induced either with an intradermal injection of olive oil in the footpad, or by an intraperitoneal injection of proteose peptone (PP). The T cell-dependent inflammation was induced by an intraperitoneal injection of the purified protein derivatives (PPD). RESULTS: While E2 inhibited olive oil-induced inflammation as monitored by the decrease in footpad swelling, it did not affect the gene expression of monocyte chemoattractant protein-1 and IL-6 by cells at the inflammatory locus. E2 also inhibited PP-induced inflammation as monitored by the decrease in the number of inflammatory peritoneal exudate cells (PEC) coinciding with a marked decrease in the number of macrophages and granulocytes (Gr. 1+). While E2 did not affect the gene expression of monocyte chemoattractant protein-1 and IL-6 by PP-elicited PEC, it decreased both gene expression and production of TNF-alpha. E2 also decreased the number of cells expressing the lymphocyte function-activated protein-1 in PP-elicited PEC, but not for CD62L. In purified protein derivative-induced T cell-dependent inflammation, E2 decreased the total cellularity of PEC and the relative numbers of CD3+ and CD4+ T cells, and the number of cells expressing the lymphocyte activation markers CD40, CD44, CD69 and IL-2Ralpha in PEC. Furthermore, while E2 did not affect the gene expression of the early T lymphocyte activation protein-1 by PEC, it decreased the gene expression of INF-gamma. CONCLUSION: Collectively, the results suggest that E2-mediated inhibition of inflammatory responses may be due to a combination of suppression of homing and activation of inflammatory cells and their production of TNF-alpha and IFN-gamma.

beta-estradiol suppresses T cell-mediated delayed-type hypersensitivity through suppression of antigen-presenting cell function and Th1 induction.

BACKGROUND: Although an immunomodulatory role for estrogens has long been demonstrated by experimental and clinical observations, the mechanism by which estrogens exert their effect on T cells has not been clearly defined. METHODS: In this study we analyzed the effects of beta-estradiol (E2), at its contraceptive dose, on the delayed-type hypersensitivity (DTH) to purified protein derivatives (PPD) and associated immune response in female mice. RESULTS: E2 treatment decreased PPD-specific DTH response, which coincided with a decrease in the leukocytes numbers in the draining lymph nodes (DLN) and spleen compared with control mice. E2 treatment also suppressed the in vitro PPD-specific proliferative response of DLN and spleen cells from PPD-primed mice. The analysis of production and gene expression of cytokines by DLN cells demonstrated that E2 treatment suppressed IL-2 and IFN-gamma production in response to PPD in vitro. In contrast, IL-4 and IL-10 gene expression by DLN cells of E2-treated mice, taken 24 h after in vivo restimulation of mice with PPD, was enhanced. Furthermore, we found that spleen APC from E2-treated mice failed to induce optimum proliferation of the PPD-primed T cells in response to PPD in vitro. The impaired APC function by E2 was not due to induction of suppressor cell activity because addition of the normal spleen APC to APC from E2-treated mice restored the proliferative response of the PPD-primed T cells in response to PPD. CONCLUSION: Our results suggest that the E2-mediated inhibition of DTH reaction is due to a combination of the down regulation of APC function and deviation of the immune response from Th1-type to Th2-type.

Beta-estradiol-induced decrease in IL-12 and TNF-alpha expression suppresses macrophage functions in the course of Listeria monocytogenes infection in mice.

Mice treated with a contraceptive dose of beta-estradiol (E2) demonstrated changes in their macrophage (Mphi) number and functions. While E2 increased and decreased the Mphi number in PBMC and PEC respectively, it enhanced the in vitro phagocytosis of FITC-labeled beads by both cells. E2 treatment also enhanced the phagocytic function of Mphi as assessed by the in vivo carbon clearance assay. In contrast, the in vitro intracellular killing function of adherent cells in peritoneal exudate cells (PEC) against Listeria monocytogenes decreased after E2 treatment. In line with the decrease in the intracellular killing function, the E2-treated mice showed an impaired protection against L. monocytogenes infection. To clarify the mechanism of the E2-mediated suppression of the protective response against L. monocytogenes infection, we next analyzed the cytokine expression by PEC in E2-treated L. monocytogenes-infected mice. On day 5 of the infection, the expression of IL-12, TNF-alpha and IL-10 by adherent PEC from the E2-treated mice was lower than that from the control-infected mice. The decrease in the cytokine expression by adherent PEC of E2-treated mice coincided with the decrease of IFN-gamma expression, and the increase in the IL-4, IL-10 and TGF-beta expressions by non-adherent PEC. These results revealed two aspects of the effects of E2 on Mphi. Even though E2 was found to enhance Mphi phagocytosis, the anti-bacterial function was suppressed. This suppression may be mediated by the inhibition of both IL-12 and TNF-alpha which play important roles in the protective response against intracellular bacteria.

[Diarrhea in urban agricultural workers in Nouakchott in Mauritania]. / La diarrhée chez les agriculteurs urbains de Nouakchott en Mauritanie.

Nearly 200 million people in the developing world are dependent or urban gardening for food and income. This practice has been accelerated by the droughts of recent decades which have forced more and more migrants into urban areas. Numerous potential health hazards have been attributed to urban gardening but the exact risks in Sahelian areas remain unclear. The purpose of this cross-sectional study was to evaluate the incidence of diarrhea at the Tel Zatar gardening site in urban Nouakchott, Mauritania. In addition, a case-control study was carried out to identify risk factors for diarrhea in function of gardeners' activity and living conditions. Statistical analysis was performed using univariate and logistical regression methods. The annual incidence of diarrhea ranged from 6.9 (IC95 p. 100 = 5.0-8.8) to 8.5 (IC95 p. 100 = 6.2-10.8) episodes per gardener and year. Multivariate analysis identified four significant risk factors. Two of these factors were unrelated to gardening, i.e., not having spent more than USD 3.50 the previous day (odds ratio (OR = 2.8, IC95 p. 100 = 1.01-7.81) and poor food hygiene (cooking outside (OR = 4.69, IC95 p. 100 = 1.06-20.83). The other two factors were regular consumption of raw vegetables (OR = 25.5, IC95 p. 100 = 2.0-32.0) and use of untreated well water (OR = 3.85, IC95 p. 100 = 1.08-14.29). Unprotected well water was the cause of 59.2 p. 100 of diarrheal episodes reported by gardeners at Tel Zatar. The results of this study confirm that vegetable production in urban gardens such as Tel Zatar is associated with health risks. Public health measures should address not only the garden sites but also domestic hygiene.