Diversity of gut microflora is required for the generation of B cell with regulatory properties in a skin graft model

B cells have been reported to promote graft rejection through alloantibody production. However, there is growing evidence that B cells can contribute to the maintenance of tolerance. Here, we used a mouse model of MHC-class I mismatched skin transplantation to investigate the contribution of B cells to graft survival. We demonstrate that adoptive transfer of B cells prolongs skin graft survival but only when the B cells were isolated from mice housed in low sterility "conventional" (CV) facilities and not from mice housed in pathogen free facilities (SPF). However, prolongation of skin graft survival was lost when B cells were isolated from IL-10 deficient mice housed in CV facilities. The suppressive function of B cells isolated from mice housed in CV facilities correlated with an anti-inflammatory environment and with the presence of a different gut microflora compared to mice maintained in SPF facilities. Treatment of mice in the CV facility with antibiotics abrogated the regulatory capacity of B cells. Finally, we identified transitional B cells isolated from CV facilities as possessing the regulatory function. These findings demonstrate that B cells, and in particular transitional B cells, can promote prolongation of graft survival, a function dependent on licensing by gut microflora

In Vivo SPECT Reporter Gene Imaging of Regulatory T Cells

Regulatory T cells (Tregs) were identified several years ago and are key in controlling autoimmune diseases and limiting immune responses to foreign antigens, including alloantigens. In vivo imaging techniques including intravital microscopy as well as whole body imaging using bioluminescence probes have contributed to the understanding of in vivo Treg function, their mechanisms of action and target cells. Imaging of the human sodium/iodide symporter via Single Photon Emission Computed Tomography (SPECT) has been used to image various cell types in vivo. It has several advantages over the aforementioned imaging techniques including high sensitivity, it allows non-invasive whole body studies of viable cell migration and localisation of cells over time and lastly it may offer the possibility to be translated to the clinic. This study addresses whether SPECT/CT imaging can be used to visualise the migratory pattern of Tregs in vivo. Treg lines derived from CD4+CD25+FoxP3+ cells were retrovirally transduced with a construct encoding for the human Sodium Iodide Symporter (NIS) and the fluorescent protein mCherry and stimulated with autologous DCs. NIS expressing self-specific Tregs were specifically radiolabelled in vitro with Technetium-99m pertechnetate (99mTcO4−) and exposure of these cells to radioactivity did not affect cell viability, phenotype or function. In addition adoptively transferred Treg-NIS cells were imaged in vivo in C57BL/6 (BL/6) mice by SPECT/CT using 99mTcO4−. After 24 hours NIS expressing Tregs were observed in the spleen and their localisation was further confirmed by organ biodistribution studies and flow cytometry analysis. The data presented here suggests that SPECT/CT imaging can be utilised in preclinical imaging studies of adoptively transferred Tregs without affecting Treg function and viability thereby allowing longitudinal studies within disease models

Dendritic cells license regulatory B cells to produce IL-10 and mediate suppression of antigen-specific CD8 T cells

Regulatory B cells (Bregs) suppress and reduce autoimmune pathology. However, given the variety of Breg subsets, the role of Bregs in the pathogenesis of type 1 diabetes is still unclear. Here, we dissect this fundamental mechanism. We show that natural protection from type 1 diabetes in nonobese diabetic (NOD) mice is associated with increased numbers of IL-10-producing B cells, while development of type 1 diabetes in NOD mice occurs in animals with compromised IL-10 production by B cells. However, B cells from diabetic mice regain IL-10 function if activated by the innate immune receptor TLR4 and can suppress insulin-specific CD8 T cells in a dendritic cell (DC)-dependent, IL-10-mediated fashion. Suppression of CD8 T cells is reliant on B-cell contact with DCs. This cell contact results in deactivation of DCs, inducing a tolerogenic state, which in turn can regulate pathogenic CD8 T cells. Our findings emphasize the importance of DC–Breg interactions during the development of type 1 diabetes

Diversity of gut microflora is required for the generation of B cell with regulatory properties in a skin graft model

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Galectin-1 is required for the regulatory function of B cells

Galectin-1 (Gal-1) is required for the development of B cells in the bone marrow (BM), however very little is known about the contribution of Gal-1 to the development of B cell regulatory function. Here, we report an important role for Gal-1 in the induction of B cells regulatory function. Mice deficient of Gal-1 (Gal-1−/−) showed significant loss of Transitional-2 (T2) B cells, previously reported to include IL-10+ regulatory B cells. Gal-1−/− B cells stimulated in vitro via CD40 molecules have impaired IL-10 and Tim-1 expression, the latter reported to be required for IL-10 production in regulatory B cells, and increased TNF-α expression compared to wild type (WT) B cells. Unlike their WT counterparts, T2 and T1 Gal-1−/− B cells did not suppress TNF-α expression by CD4+ T cells activated in vitro with allogenic DCs (allo-DCs), nor were they suppressive in vivo, being unable to delay MHC-class I mismatched skin allograft rejection following adoptive transfer. Moreover, T cells stimulated with allo-DCs show an increase in their survival when co-cultured with Gal-1−/− T2 and MZ B cells compared to WT T2 and MZ B cells. Collectively, these data suggest that Gal-1 contributes to the induction of B cells regulatory function

Lateral Flow Immunoassays for Detecting Viral Infectious Antigens and Antibodies

Abundant immunological assays currently exist for detecting pathogens and identifying infected individuals, making detection of diseases at early stages integral to preventing their spread, together with the consequent emergence of global health crises. Lateral flow immunoassay (LFIA) is a test characterized by simplicity, low cost, and quick results. Furthermore, LFIA testing does not need well-trained individuals or laboratory settings. Therefore, it has been serving as an attractive tool that has been extensively used during the ongoing COVID-19 pandemic. Here, the LFIA strip’s available formats, reporter systems, components, and preparation are discussed. Moreover, this review provides an overview of the current LFIAs in detecting infectious viral antigens and humoral responses to viral infections

AKAL DAN WAHYU MENURUT MUSA ASY’ARIE

Dengan akal manusia mampu membedakan mana yang hak dan yang batil, mana yang benar dan mana yang salah. Sebagaimana Al-Qur‘an memang merupakan suatu sumber kebenaran mutlak yang bersumber dari Tuhan. Namun kebenaran Al-Qur‘an tidak hanya bersifat Internal bagi dirinya sendiri, tetapi yang lebih penting lagi adalah makna eksternalnya, sebagai pedoman bagi kehidupan manusia. Islam sebagai agama yang bersandar pada wahyu, yaitu Al-Qur‘an pada dasarnya menuntut pemeluknya untuk dapat berdialog dengan wahyu itu, dengan menggunakan kapasitas akalnya secara optimal dalam memahami wahyu. Kedua hal ini hendaknya memiliki hubungan yang bersifat fungsional, agar manusia mampu berdialog dengan wahyu dalam upaya menjadikan wahyu sebagai pedoman hidup bagi manusia. Jika akal dan wahyu memiliki hubungan secara struktural, artinya wahyu di atas akal, atau sebaliknya akal di atas wahyu. Sehingga salah satu dari keduanya mensubordinasi yang lainnya, maka akan membawa kesulitan munculnya dinamika fungsional keduanya. Hubungan yang bersifat struktural tidak bisa diterapkan dalam memahami wahyu. Karena wahyu tidak bisa dipahami secara benar, dan akal tidak bisa memahami kebenaran yang hakiki tanpa adanya wahyu. Musa Asy‘arie dalam bukunya Islam Etos Kerja dan Pemberdayaan Ekonomi Umat menjelaskan akal dan wahyu pada tahap dialog, akal berhubungan secara fungsional dengan wahyu, bukan hubungan atas struktural atas-bawah. Dalam penelitian ini, penulis menggunakan metode penelitian kepustakaan (Library Research) yang bersifat deskriptif-analisis. Metode deskriptif digunakan untuk membuat deskripsi, gambaran atau melukiskan hubungan-hubungan dari sebuah data, kemudian dilanjutkan dengan metode analisis, untuk menganalisis data, kemudian mereduksi, melakukan penafsiran dan interpretasi serta menarik kesimpulan. Dalam penelitian ini sebuah data diolah dan digali dari berbagai buku, surat kabar, majalah, makalah, berbagai literatur yang berkaitan dengan tema penelitian ini dan tentunya sebagai data primer juga wawancara terhadap narasumber, yakni Musa Asy‘arie sendiri. Al-Qur‘an sebagai pedoman hidup bagi manusia menyiratkan secara tegas adanya hubungan fungsional, dan menolak hubungan struktural, karena jika antara akal dan wahyu memiliki hubungan struktural, maka akal tidak bisa berfungsi kreatif dalam memahami Al-Quran sebagai pedoman hidup. Sehingga pemahaman dan penafsiran secara kreatif terhadap wahyu menjadikan mutlak diperlukan, agar segala firman-firman Tuhan yang terkandung di dalam Al-Quran bisa dijadikan pedoman hidup, dan sebagai jawaban bagi persoalan-persoalan yang dihadapi oleh manusia. Baik secara langsung, dengan memfirmankan di dalam Al-Qur‘an, atau secara tidak langsung, dimana wahyu memberikan inspirasi kreatif dalam pemecahan persoalan yang ada

Seroprevalence of SARS-CoV-2 Binding and Neutralizing Antibodies in Healthcare Workers during the Epidemic Peak in Referral Hospitals and Quarantine Sites: Saudi Arabia

Healthcare workers (HCWs) are at high risk for SARS-CoV-2 infection compared to the general population. Here, we aimed to evaluate and characterize the SARS-CoV-2 seropositivity rate in randomly collected samples among HCWs from the largest referral hospitals and quarantine sites during the peak of the COVID-19 epidemic in the city of Jeddah, the second largest city in Saudi Arabia, using a cross-sectional analytic study design. Out of 693 participants recruited from 29 June to 10 August 2020, 223 (32.2%, 95% CI: 28.8–35.8) were found to be confirmed seropositive for SARS-CoV-2 antibodies, and among those 197 (88.3%) had never been diagnosed with COVID-19. Seropositivity was not significantly associated with participants reporting COVID-19 compatible symptoms as most seropositive HCW participants 140 (62.8%) were asymptomatic. The large proportion of asymptomatic SARS-CoV-2 cases detected in our study demands periodic testing as a general hospital policy