Tumor cells are thought to evade immune surveillance through interaction with immune cells. Much recent attention has focused on the modification of immune responses as a basis for new cancer treatments. SIRPα is an Ig superfamily protein that inhibits phagocytosis in macrophages upon interaction with its ligand CD47 expressed on the surface of target cells. Here, we show that SIRPα is highly expressed in human renal cell carcinoma and melanoma. Furthermore, an anti-SIRPα Ab that blocks the interaction with CD47 markedly suppressed tumor formation by renal cell carcinoma or melanoma cells in immunocompetent syngeneic mice. This inhibitory effect of the Ab appeared to be mediated by dual mechanisms: direct induction of Ab-dependent cellular phagocytosis of tumor cells by macrophages and blockade of CD47-SIRPα signaling that negatively regulates such phagocytosis. The antitumor effect of the Ab was greatly attenuated by selective depletion not only of macrophages but also of NK cells or CD8 ⁺ T cells. In addition, the anti-SIRPα Ab also enhances the inhibitory effects of Abs against CD20 and programmed cell death 1 (PD-1) on tumor formation in mice injected with SIRPα-nonexpressing tumor cells. Anti-SIRPα Abs thus warrant further study as a potential new therapy for a broad range of cancers.

The successful establishment of the wMel strain of Wolbachia for the control of arbovirus transmission by Aedes aegypti has been proposed and is being implemented in a number of countries. Here we describe the successful establishment of the wMel strain of Wolbachia in four sites in Yogyakarta, Indonesia. We demonstrate that Wolbachia can be successfully introgressed after transient releases of wMel-infected eggs or adult mosquitoes. We demonstrate that the approach is acceptable to communities and that Wolbachia maintains itself in the mosquito population once deployed. Finally, our data show that spreading rates of Wolbachia in the Indonesian setting are slow which may reflect more limited dispersal of Aedes aegypti than seen in other sites such as Cairns, Australia. We show that the wMel strain of Wolbachia can be deployed successfully into mosquito populations in an area of intense dengue transmission in Yogyakarta, Indonesia. Deployment was achieved through either the release of eggs or adult mosquitoes with full community support. This represents the successful first step toward a large trial to evaluate the use of Wolbachia in Indonesia to disrupt transmission of arboviruses such as dengue, Zika and chikungunya.

Indonesia is one of the countries where dengue infection is prevalent. In this study we measure the prevalence and distribution of dengue virus (DENV) DENV-infected Aedes aegypti in Yogyakarta City, Indonesia, during the wet season when high dengue transmission period occurred, as baseline data before implementation of a Wolbachia-infected Aedes aegypti trial for dengue control. We applied One-Step Multiplex Real Time PCR (RT-PCR) for the type-specific-detection of dengue viruses in field-caught adult Aedes aegypti mosquitoes. In a prospective field study conducted from December 2015 to May 2016, adult female Aedes aegypti were caught from selected areas in Yogyakarta City, and then screened by using RT-PCR. During the survey period, 36 (0.12%) mosquitoes from amongst 29,252 female mosquitoes were positive for a DENV type. In total, 22.20% of dengue-positive mosquitoes were DENV-1, 25% were DENV-2, 17% were DENV-3, but none were positive for DENV-4. This study has provided dengue virus infection prevalence in field-caught Aedes aegypti and its circulating serotype in Yogyakarta City before deployment of Wolbachia-infected Aedes aegypti.

Background: Growing evidence shows that viral co-infection is found repeatedly in patients with Coronavirus Disease-2019 (COVID-19). This is the first report of SARS-CoV-2 co-infection with viral respiratory pathogens in Indonesia. Methods: Over a one month period of April to May 2020, SARS-CoV-2 positive nasopharyngeal swabs in our COVID-19 referral laboratory in Yogyakarta, Indonesia, were tested for viral respiratory pathogens by real-time, reverse transcription polymerase chain reaction (RT-PCR). Proportion of co-infection reported in percentage. Results: Fifty-nine samples were positive for other viral respiratory pathogens among a total of 125 samples. Influenza A virus was detected in 32 samples, Influenza B in 16 samples, Human metapneumovirus in 1 sample, and adenovirus in 10 samples. We did not detect any co-infection with respiratory syncytial virus. Nine (7.2%) patients had co-infection with more than two viruses. Conclusion: Viral co-infection with SARS-CoV-2 is common. These results will provide a helpful reference for diagnosis and clinical treatment of patients with COVID-19.

High mobility group box 1 (HMGB1) and interleukin-18 (IL-18) are involved in various non-coronavirus disease pathogenesis and are reported as potential biomarkers for coronavirus disease (COVID-19). However, their association with COVID-19 pathogenesis has not yet been explored. This study aimed to investigate the association between HMGB1 and IL-18 concentrations in the sera of COVID-19 patients versus non-COVID-19 patients. We used stored serum samples obtained from 30 COVID-19 patients and 30 non-COVID-19 patients. We collected data on age, gender, treatment status, principal diagnosis, and comorbidity from patient medical records. HMGB1 and IL-18 concentrations were analyzed in the serum by enzyme-linked immunosorbent assay (ELISA). The swab samples' RT-PCR cycle threshold (CT) values were obtained from the laboratory database. HMGB1 concentrations were increased in the COVID-19 inpatients and non-COVID-19 inpatients compared to non-COVID-19 outpatients (COVID-19 inpatients vs. non-COVID-19 outpatients: 151.33 (90.27-192.38) vs. 80.75 (54.16-128.72) ng/ml; p = 0.0316; non-COVID-19 inpatients vs. non-COVID-19 outpatients: 152.66 (104.04-288.51) vs. 80.75 (54.16-128.72) ng/ml; p = 0.0199). IL-18 concentrations were also higher in the COVID-19 inpatients and non-COVID-19 inpatients compared to non-COVID-19 outpatients (COVID-19 inpatients vs. non-COVID-19 outpatients: 620.00 (461.50-849.6) vs. 403.10 (372.70-556.90) pg/ml; p = 0.0376; non-COVID-19 inpatients vs. non-COVID-19 outpatients: 835.70 (558.30-1602.00) vs. 403.10 (372.70-556.90) pg/ml; p = 0.0026). Moreover, HMGB1 was associated with IL-18 concentrations in the sera of COVID-19 inpatients (p = 0.0337; r = 0.5500). The association of HMGB1 and IL-18 in COVID-19 might indicate the potential for a dangerous cycle leading to a cytokine storm to occur.

Rovik A, Daniwijaya EW, Supriyati E, Rahayu A, Kumalawati DA, Saraswati U, Handayaningsih AE, Rachman MP, Oktriani R, Kurniasari I, Candrasari DS, Nurhayati I, Sholeh R, Arianto B, Tantowijoyo W, Ahmad RA, Utarini A, Arguni E. 2022. Wolbachia genetic similarity in different insect host species: Drosophila melanogaster and Yogyakarta’s (Indonesia) Aedes aegypti as a novel host. Biodiversitas 23: 2321-2328. Wolbachia naturally presents in a large number of insects and other arthropod species. The Wolbachia strain wMel from Drosophila melanogaster has been stably transinfected into Aedes aegypti where it stops the mosquito host from being infected with medically important arbovirus like dengue. Consequently, Ae. aegypti infected with wMel have been released in Indonesia as a public health intervention against dengue. This study genetically compared wMel from Yogya field-caught D. melanogaster and the wMel in stably transfected Ae. aegypti used for field releases in Yogyakarta, Indonesia. The genetic similarity between wMel Wolbachia was evaluated by sequencing of Wolbachia surface protein (wsp) gene and some polymorphic genomic regions of insertion sites (IS) and variable number tandem repeats (VNTR) loci. The sequence of the Wolbachia surface protein (wsp) gene was 100% identical between hosts. There is no insertion sequence among specimens. The insertion sequence IS-WD1310 was identical between wMel from both hosts and among other strains, as well as the IS-WD516/7. The VNTR-141 period was identical within wMel from both hosts and among other strains, the VNTR-105 as well. Wolbachia Yogya field-caught D. melanogaster and Wolbachia strain wMel present in Ae. aegypti used for bio-control of dengue were genetically identical. These findings provide beneficial understanding to answer the public attention on safety issues, especially on the genetic similarity between Wolbachia strain in the natural and transfected hosts of this novel technology for dengue control.