Porcine TRIM21 Enhances Porcine Circovirus 2 Infection and Host Immune Responses, But Inhibits Apoptosis of PCV2-Infected Cells

Tripartite motif protein 21 (TRIM21) is an interferon-inducible E3 ligase, containing one RING finger domain, one B-box motif, one coiled-coil domain at the N-terminal, as well as one PRY domain and one SPRY domain at the C-terminal. TRIM21 is expressed in many tissues and plays an important role in systemic autoimmunity. However, TRIM21 plays different roles in different virus infections. In this study, we evaluate the relationship between porcine TRIM21 and PCV2 infection as well as host immune responses. We found that PCV2 infection modulated the expression of porcine TRIM21. TRIM21 can enhance interferons and proinflammatory factors and decrease cellular apoptosis in PCV2-infected cells. These results indicate that porcine TRIM21 plays a critical role in enhancing PCV2 infection, which is a promising target for controlling and developing the treatment of PCV2 infection.

AAV11 permits efficient retrograde targeting of projection neurons

Viral tracers that permit efficient retrograde targeting of projection neurons are powerful vehicles for structural and functional dissections of the neural circuit and for the treatment of brain diseases. Recombinant adeno-associated viruses (rAAVs) are the most potential candidates because they are low-toxic with high-level transgene expression and minimal host immune responses. Currently, some rAAVs based on capsid engineering for retrograde tracing have been widely used in the analysis and manipulation of neural circuits, but suffer from brain area selectivity and inefficient retrograde transduction in certain neural connections. Here, we discovered that the recombinant adeno-associated virus 11 (rAAV11) exhibits potent retrograde labeling of projection neurons with enhanced efficiency to rAAV2-retro in some neural connections. Combined with calcium recording technology, rAAV11 can be used to monitor neuronal activities by expressing Cre recombinase or calcium-sensitive functional probe. In addition, we further showed the suitability of rAAV11 for astrocyte targeting. These properties make rAAV11 a promising tool for the mapping and manipulation of neural circuits and gene therapy of some neurological and neurodegenerative disorders.

Piperlongumine Is an NLRP3 Inhibitor With Anti-inflammatory Activity

Piperlongumine (PL) is an alkaloid from Piper longum L. with anti-inflammatory and antitumor properties. Numerous studies have focused on its antitumor effect. However, the underlying mechanisms of its anti-inflammation remain elusive. In this study, we have found that PL is a natural inhibitor of Nod-like receptor family pyrin domain-containing protein-3 (NLRP3) inflammasome, an intracellular multi-protein complex that orchestrates host immune responses to infections or sterile inflammations. PL blocks NLRP3 activity by disrupting the assembly of NLRP3 inflammasome including the association between NLRP3 and NEK7 and subsequent NLRP3 oligomerization. Furthermore, PL suppressed lipopolysaccharide-induced endotoxemia and MSU-induced peritonitis in vivo, which are NLRP3-dependent inflammation. Thus, our study identified PL as an inhibitor of NLRP3 inflammasome and indicated the potential application of PL in NLRP3-relevant diseases.

Antibiotics in early life and childhood pre-B-ALL. Reasons to analyze a possible new piece in the puzzle

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer with precursor B-cell ALL (pB-ALL) accounting for ~ 85% of the cases. Childhood pB-ALL development is influenced by genetic susceptibility and host immune responses. The role of the intestinal microbiome in leukemogenesis is gaining increasing attention since Vicente-Dueñas’ seminal work demonstrated that the gut microbiome is distinct in mice genetically predisposed to ALL and that the alteration of this microbiome by antibiotics is able to trigger pB-ALL in Pax5 heterozygous mice in the absence of infectious stimuli. In this review we provide an overview on novel insights on the role of the microbiome in normal and preleukemic hematopoiesis, inflammation, the effect of dysbiosis on hematopoietic stem cells and the emerging importance of the innate immune responses in the conversion from preleukemic to leukemic state in childhood ALL. Since antibiotics, which represent one of the most widely used medical interventions, alter the gut microbial composition and can cause a state of dysbiosis, this raises exciting epidemiological questions regarding the implications for antibiotic use in early life, especially in infants with a a preleukemic “first hit”. Sheading light through a rigorous study on this piece of the puzzle may have broad implications for clinical practice.

The Mycobacterium tuberculosis PE_PGRS Protein Family Acts as an Immunological Decoy to Subvert Host Immune Response

Mycobacterium tuberculosis (M.tb) is a successful pathogen that can reside within the alveolar macrophages of the host and can survive in a latent stage. The pathogen has evolved and developed multiple strategies to resist the host immune responses. M.tb escapes from host macrophage through evasion or subversion of immune effector functions. M.tb genome codes for PE/PPE/PE_PGRS proteins, which are intrinsically disordered, redundant and antigenic in nature. These proteins perform multiple functions that intensify the virulence competence of M.tb majorly by modulating immune responses, thereby affecting immune mediated clearance of the pathogen. The highly repetitive, redundant and antigenic nature of PE/PPE/PE_PGRS proteins provide a critical edge over other M.tb proteins in terms of imparting a higher level of virulence and also as a decoy molecule that masks the effect of effector molecules, thereby modulating immuno-surveillance. An understanding of how these proteins subvert the host immunological machinery may add to the current knowledge about M.tb virulence and pathogenesis. This can help in redirecting our strategies for tackling M.tb infections.

Pneumococcal Surface Protein A: A Promising Candidate for the Next Generation of Pneumococcal Vaccines

Streptococcus pneumoniae is the bacterium that causes pneumococcal disease which often results in pneumonia, meningitis, otitis media, septicemia and sinusitis. Pneumonia, particularly, is a significant cause of worldwide morbidity and a global health burden as well. Treatment often relies on antimicrobials, to which the pathogen is frequently mutating and rendering infective. Consequently, vaccination is the most effective approach in dealing with pneumococcal antimicrobial resistance (AMR). Unfortunately, the current pneumococcal polysaccharide and conjugate vaccines have a narrow serotype coverage. Therefore, the current need for vaccines with a broader serotype coverage cannot be overstated. Pneumococcal Surface Protein A and C are potential vaccine candidate antigens present in over 90% of the strains from clinical isolates as well as laboratory non-encapsulated strains. Pneumococcal Surface Protein A is an active virulent factor that pneumococci use to evade complement-mediated host immune responses and has been shown to elicit immune responses against pneumococcal infections. This review explores the potential utilization of Pneumococcal Surface Protein A to immunize against S. pneumoniae.

First person – Ziyan Fang

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Ziyan Fang is first author on ‘ The Salmonella effector SifA initiates a kinesin-1 and kinesin-3 recruitment process mirroring that mediated by Arl8a and Arl8b’, published in JCS. Ziyan conducted the research described in this article while a PhD student in Stéphane Méresse's lab at Centre d'Immunologie de Marseille-Luminy (CIML), Marseille, France. She is now a postdoc in the lab of Elina Zúñiga at Division of Biological Sciences, University of California, USA, where her research interests lie in studying the cellular and molecular aspects of the host immune responses during viral or bacterial infection.

Vaccine-breakthrough infection by the SARS-CoV-2 Omicron variant elicits broadly cross-reactive immune responses

Highly transmissible SARS-CoV-2 Omicron variant has posted a new crisis for COVID-19 pandemic control. Within a month, Omicron is dominating over Delta variant in several countries probably due to immune evasion. It remains unclear whether vaccine-induced memory responses can be recalled by Omicron infection. Here, we investigated host immune responses in the first vaccine-breakthrough case of Omicron infection in Hong Kong. We found that the breakthrough infection rapidly recruited potent cross-reactive broad neutralizing antibodies (bNAbs) against current VOCs, including Alpha, Beta, Gamma, Delta and Omicron, from unmeasurable IC50 values to mean 1:2929 at around 9-12 days, which were higher than the mean peak IC50 values of BioNTech-vaccinees. Cross-reactive spike- and nucleocapsid-specific CD4 and CD8 T cell responses were detected. Similar results were also obtained in the second vaccine-breakthrough case of Omicron infection. Our preliminary findings may have timely implications to booster vaccine optimization and preventive strategies of pandemic control.