CCR6 expression reduces mouse survival upon malarial challenge with Plasmodium berghei NK65 strain

BACKGROUND It has been demonstrated that proteins expressed by liver-stage Plasmodium parasites can inhibit the translocation of transcription factors to the nucleus of different cells. This process would hinder the expression of immune genes, such as the CCL20 chemokine. OBJECTIVE Since CCR6 is the only cognate receptor for CCL20, we investigated the importance of this chemokine-receptor axis against rodent malaria. METHODS CCR6-deficient (KO) and wild-type (WT) C57BL/6 mice were challenged with Plasmodium berghei (Pb) NK65 sporozoites or infected red blood cells (iRBCs). Liver parasitic cDNA, parasitemia and serum cytokine concentrations were respectively evaluated through reverse transcription-polymerase chain reaction (RT-PCR), staining thin-blood smears with Giemsa solution, and enzyme-linked immunosorbent assay (ELISA). FINDINGS Although the sporozoite challenges yielded similar liver parasitic cDNA and parasitemia, KO mice presented a prolonged survival than WT mice. After iRBC challenges, KO mice kept displaying higher survival rates as well as a decreased IL-12 p70 concentration in the serum than WT mice. CONCLUSION Our data suggest that malaria triggered by PbNK65 liver- or blood-stage forms elicit a pro-inflammatory environment that culminates with a decreased survival of infected C57BL/6 mice.

La Toxoplasmosis observada como un problema no resuelto / Toxoplasmosis: an unsolved problem

Un tercio de la población mundial poseen anticuerpos contra Toxoplasma gondii. El hombre se infecta a través de los esporozoitos provenientes de las heces de los gatos que contaminan la tierra, frutas, verduras y al agua; de los bradizoitos presentes en carnes que lo infectan cuando la consume poco cocinada o por su manipulación y por trofozoitos circulantes durante la fase hematógena en el hombre, infecta al feto a través de la placenta y a individuos seronegativos por órganos sólidos trasplantados o transfundidos con elementos formes de la sangre; son los llamados grupos de riesgos los más vulnerables a desarrollar formas graves de esta enfermedad que los puede conducir a la muerte. Estudios resientes corroboran la relación de esta infección con trastornos neurosiquiatricos, en particular con la esquizofrenia, así como su relación con accidentes de tránsito en conductores seropositivos; es de gran importancia tener presente las formas de adquirir la enfermedad y las medidas de precaución sobre todo cuando se ha demostrado que nunca se ha padecido la enfermedad.

One third of the world population have antibodies against Toxoplasma gondii. Human beings may be infected by sporozoites from cat faeces contaminating the ground, fruits, vegetables and water, by bradyzoites present in insufficiently cooked or improperly manipulated meat, or by trophozoites circulating during the hematogenous phase. Fetuses may be infected through the placenta, and seronegative individuals by solid organs transplanted or transfused with formed elements of the blood. These are the risk groups most prone to develop serious, life-threatening forms of the disease. Recent studies confirm the relationship of this infection to neuropsychiatric disorders, particularly schizophrenia, as well as its relationship to traffic accidents among seropositive drivers. It is paramount to bear in mind the ways in which the disease may be acquired and the corresponding prevention measures, especially for persons who have never had the disease.

Antitumor effect of malaria genetically attenuated sporozoites infection in a murine lewis lung cancer model / 重庆医学

Objective To learn whether plasmodium genetic attenuated sporozoites (GAS) can induce immunity against lung cancer ,in order to provide new ideas for the study of lung cancer vaccine .Methods Ther study was divided into two groups respec‐tively ,experimental group received intravenous injection of genetically attenuated sporozoites to immunize C57BL/6J mice and con‐trol group injection of phosphate buffer solution (PBS);after 14 days ,we subcutaneously inoculated lewis lung cancer (LLC) cells , calipers was used to measure tumor size .Immunohistochemical staining was detected tumor proliferation ,apoptosis ,and angiogene‐sis .Results There was statistically significant in tumor size .Immunohistochemical staining revealed that attenuated sporozoites in‐fection inhibited LLC eslls proliferation ,angiogenesis ,apoptosis .Conclusion The malaria attenuated sporozoites may provide a no‐vel strategy or therapeutic vaccine vector for anti‐lung cancer immune‐based therapy .

High-throughput virtual screening for novel dhfr inhibitors of P. Jiroveci from the zinc database.

Many of the opportunistic infections that occur at this late stage can be fatal and since that Pneumocystis carinii pneumonia (PCP) is a leading opportunistic infection found among immunocompromised (CD4 cell < 200) patients worldwide. DHFR is responsible for the growth and maturation of sporozoites stage (life cycle) in Pneumocystis as reported. Currently, 13 million chemical compounds are available for virtual screening in ZINC database. The biological information of four known drug molecules like TMP/SMX, Dapsone, Atovaquone and Pentamidine were collected from the PubChem compound database. Q-Site Finder online tool was used to determine the active site of DHFR in P. jiroveci. LogP values of chemical compounds were identified with the Atom-additive method. Since, existing drugs are synthetic chemicals that give more side effects in Pneumocystis affected patients. Polar surface area value of oxamide (86.18) was predicted to be in the ranges of existing drug values. Pentamidine was proved to be a more efficient ligand based on the dock score of -26.3398 still could not be considered as the natural compound oxamide also was highly comparable with the value of -20.3173. The binding affinity of the selected molecule was analyzed through Pose View and LigPlot.

Induction and maintenance of protective CD8+ T cells against malaria liver stages: implications for vaccine development

CD8+ T cells against malaria liver stages represent a major protective immune mechanism against infection. Following induction in the peripheral lymph nodes by dendritic cells (DCs), these CD8+ T cells migrate to the liver and eliminate parasite infected hepatocytes. The processing and presentation of sporozoite antigen requires TAP mediated transport of major histocompatibility complex class I epitopes to the endoplasmic reticulum. Importantly, in DCs this process is also dependent on endosome-mediated cross presentation while this mechanism is not required for epitope presentation on hepatocytes. Protective CD8+ T cell responses are strongly dependent on the presence of CD4+ T cells and the capacity of sporozoite antigen to persist for a prolonged period of time. While human trials with subunit vaccines capable of inducing antibodies and CD4+ T cell responses have yielded encouraging results, an effective anti-malaria vaccine will likely require vaccine constructs designed to induce protective CD8+ T cells against malaria liver stages.

Detection of Plasmodium vivax sporozoites-carrying mosquitoes using loop-mediated isothermal amplification (LAMP) / 中国血吸虫病防治杂志

Objective To establish a simple,convenient,quick and high sensitive method of loop-mediated isothermal amplification (LAMP) for detection of Plasmodium vivax-carrying mosquitoes.Methods The species conservative regions of P.v CSP gene were selected to design 2 pairs of primers which recognized 6 distinct regions.To evaluate the specificity of detection by LAMP,infected Anopheles,An.sinensis (An.s),Plasmodium falciparum (P.f),and healthy human blood DNA were selected as templates.To assess the sensitivity of detection,1.3×10~6,1.3×10~5,1.3×10~4,1.3×10~3,1.3×10~2,1.3×10~1 and 1.3×10~0 copies of P.v CSP plasmid DNA mixed with 1.0 μl An.s DNA were used as the templates of LAMP.The infected An.s DNAs were diluted with negative An.s DNA by 1:2,1:4,1:8,1:16,1:32,1:64,1:128 and 1:256 and then detected by LAMP to show the sensitivity of batch quantity detection.The applied value of this method was evaluated by detecting the same batch of 67 artificial infected An.s mosquitoes,and compared with the detection of microscopic examination and nested PCR in parallel.Results By using LAMP,the detection of infected An.s was positive,while the control samples were all negative.The limits of detection of different proportion dilutions of the mixture of P.v CSP plasmid DNA with An.s DNA were 1.3×10~2 copies.The limits of detection of different proportion dilutions of the mixture of infected An.s DNA with An.s DNA were 1:128.The positive rate of detecting the same batch of 67 artificial infected mosquitoes was 47.76% by LAMP,25.37% by the microscopic examination (X~2 = 7.24,P0.05).Compared with the test of the microscopic examination and then with a statistical analysis,the sensitivity of LAMP was 100%,which agreed well with the sensitivity of nested PCR (100%).Conclusion The method of LAMP is simple,convenient and high sensitive,and it is a potential method for detecting Plasmodium vivax-carrying mosquitoes in the field.

Detection of P.falciparum and P.vivax sporozoites in mosquitoes by ELISA

A total of 10.140 Anopheles mosquitoes were collected during the period 1985-1995 in 5 study sites. ELISA(+) reactions were detected in 229 mosquito samples from 10 Anopheles species of An.minimus, An.dirus, An.vagns, An.maculatus, An.subpictus, An.campestris, An.tessellatus, An.jeyporiensis, An.aconitus, An.spl. In Bai Tranh (Thanh Hoa province), Khanh Phu and Khanh Nam (Khanh Hoa province), 7 species were found to be infected with malaria sporozoites as An.minimus, An.dirus, An.vagus, An.maculatus. An.aconitus, An.tessellatus, An.jeyporiensis. In the brackish water commune Phong Phu (Binh Chanh district, HCM city) and in Can Giuoc district (Long An province), 7 species were found to be infected with malaria sporozoites as An. subpictus, An.sinensis, An.sundaicus, An.campestris, An.vagus, An.tessellatuss, An.spl. The positive infection rate was An.dirus (4,5% - 8,5%), An.minimus (8,3%) in Khanh Phu and Khanh Nam (Khánh Hòa) and An.sinensis (4,5% - 11%). An.campestris (6,6% - 6,7%), An.vagus (4,6%) in Phong Phu (HCM city) and Can Giuoc (Long An)

Sporozoites of plasmodium sp. in anopheles mangyanus and oocysts in A. kochi

Dissections of anopheles mosquitoes in Tabla Valley, Cauayan, Occidental Negros (Philippines), conducted to determine the existence of malaria vectors other than A. minimus flavirostris in the Philippines, showed the following results: 1) Oocysts and sporozoites were found in A. mangyanus2) Infected guts and glands in A. minimus flavirostris were also demonstrated3) Oocysts were found in A. kochiAlthough it was not possible to ascertain if the sporozoites and oocysts found were those of human, avian or simian malaria, there is a strong presumption to incriminate A. mangyanus as a vector of human malaria in the Philippines. (Summary)