Helminth-derived proteins as immune system regulators: a systematic review of their promise in alleviating colitis.

Helminth-derived proteins have immunomodulatory properties, influencing the host's immune response as an adaptive strategy for helminth survival. Helminth-derived proteins modulate the immune response by inducing anti-inflammatory cytokines, promoting regulatory T-cell development, and ultimately favouring a Th2-biased immune response. This systematic review focused on helminth-derived proteins and explored their impact on reducing inflammatory responses in mouse models of colitis. A systematic search across Medline, EMBASE, Web of Science, and Cochrane Library identified fourteen relevant studies. These studies reported immunomodulatory changes, including increased production of anti-inflammatory cells and cytokines. In mouse models of colitis treated with on helminth-derived proteins, significant improvements in pathological parameters such as body weight, colon length, and microscopic inflammatory scores were observed compared to control groups. Moreover, helminth-derived proteins can enhance the function of Tregs and alleviate the severity of inflammatory conditions. The findings underscore the pivotal role of helminth-derived proteins in immunomodulation, specifically in the axis of cytokine secretion and immune cell polarization. The findings offer new opportunities for treating chronic inflammatory conditions such Crohn's disease.

The role of ß2 integrin in dendritic cell migration during infection.

BACKGROUND: Dendritic cells (DCs) play a key role in shaping T cell responses. To do this, DCs must be able to migrate to the site of the infection and the lymph nodes to prime T cells and initiate the appropriate immune response. Integrins such as ß2 integrin play a key role in leukocyte adhesion, migration, and cell activation. However, the role of ß2 integrin in DC migration and function in the context of infection-induced inflammation in the gut is not well understood. This study looked at the role of ß2 integrin in DC migration and function during infection with the nematode worm Trichuris muris. Itgb2tm1Bay mice lacking functional ß2 integrin and WT littermate controls were infected with T. muris and the response to infection and kinetics of the DC response was assessed. RESULTS: In infection, the lack of functional ß2 integrin significantly reduced DC migration to the site of infection but not the lymph nodes. The lack of functional ß2 integrin did not negatively impact T cell activation in response to T. muris infection. CONCLUSIONS: This data suggests that ß2 integrins are important in DC recruitment to the infection site potentially impacting the initiation of innate immunity but is dispensible for DC migration to lymph nodes and T cell priming in the context of T. muris infection.

The importance of combining serological testing with RT-PCR assays for efficient detection of COVID-19 and higher diagnostic accuracy.

Misdiagnosing suspected COVID-19 individuals could largely contribute to the viruses transmission, therefore, making an accurate diagnosis of infected subjects vital in minimizing and containing the disease. Although RT-PCR is the standard method in detecting COVID-19, it is associated with some limitations, including possible false negative results. Therefore, serological testing has been suggested as a complement assay to RT-PCR to support the diagnosis of acute infections. In this study, 15 out of 639 unvaccinated healthcare workers (HCWs) were tested negative for COVID-19 by RT-PCR and were found seropositive for SARS-CoV-2 nucleocapsid protein-specific IgM and IgG antibodies. These participants underwent additional confirmatory RT-PCR and SARS-CoV-2 spike-specific ELISA tests. Of the 15 individuals, nine participants were found negative by second RT-PCR but seropositive for anti-spike IgM and IgG antibodies and neutralizing antibodies confirming their acute infection. At the time of collection, these nine individuals were in close contact with COVID-19-confirmed patients, with 77.7% reporting COVID-19-related symptoms. These results indicate that including serological tests in the current testing profile can provide better outcomes and help contain the spread of the virus by increasing diagnostic accuracy to prevent future outbreaks rapidly.

Robust memory humoral immune response to SARS-CoV-2 in the tonsils of adults and children.

Background: Adaptive humoral immunity against SARS-CoV-2 has mainly been evaluated in peripheral blood. Human secondary lymphoid tissues (such as tonsils) contain large numbers of plasma cells that secrete immunoglobulins at mucosal sites. Yet, the role of mucosal memory immunity induced by vaccines or natural infection against SARS-CoV-2 and its variants is not fully understood. Methods: Tonsillar mononuclear cells (TMNCs) from adults (n=10) and children (n=11) were isolated and stimulated using positive SARS-CoV-2 nasal swabs. We used endpoint enzyme-linked immunosorbent assays (ELISAs) for the measurement of anti-S1, -RBD, and -N IgG antibody levels and a pseudovirus microneutralization assay to assess neutralizing antibodies (nAbs) in paired serum and supernatants from stimulated TMNCs. Results: Strong systemic humoral response in previously SARS-CoV-2 infected and vaccinated adults and children was observed in accordance with the reported history of the participants. Interestingly, we found a significant increase in anti-RBD IgG (305 and 834 folds) and anti-S1 IgG (475 and 443 folds) in the stimulated TMNCs from adults and children, respectively, compared to unstimulated cells. Consistently, the stimulated TMNCs secreted higher levels of nAbs against the ancestral Wuhan strain and the Omicron BA.1 variant compared to unstimulated cells by several folds. This increase was seen in all participants including children with no known history of infection, suggesting that these participants might have been previously exposed to SARS-CoV-2 and that not all asymptomatic cases necessarily could be detected by serum antibodies. Furthermore, nAb levels against both strains were significantly correlated in adults (r=0.8788; p = 0.0008) and children (r = 0.7521; p = 0.0076), and they strongly correlated with S1 and RBD-specific IgG antibodies. Conclusion: Our results provide evidence for persistent mucosal humoral memory in tonsils from previously infected and/or vaccinated adults and children against recent and old variants upon re-exposure. They also highlight the importance of targeting mucosal sites with vaccines to help control infection at the primary sites and prevent potential breakthrough infections.