Immune proteasomes and immunity

A lot of facts that require understanding have been accumulated since immune proteasomes were discovered and their relationship with the immune response was established. For example, why are immune proteasomes present in all studied mammalian organs and tissues, including nonlymphoid tissues? What is responsible for differences in the ratio of immune to constitutive proteasomes in different organs? Are the functions of immune proteasomes related to the immune response alone, as was shown initially, or not? Are immune proteasomes formed simultaneously in different organs during ontogenesis? An attempt is made in this review to answer these and other related questions.     

Spliceosome-targeted therapies trigger an antiviral immune response in triple-negative breast cancer

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A defective viral genome strategy elicits broad protective immunity against respiratory viruses

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Immune Checkpoint Blockade Augments Changes Within Oncolytic Virus-induced Cancer MHC-I Peptidome,Creating Novel Antitumor CD8 T Cell Reactivities

The combination cancer immunotherapies with oncolytic virus (OV) and immune checkpoint blockade (ICB) reinstate otherwise dysfunctional antitumor CD8 T cell responses. One major mechanism that aids such reinstatement of antitumor CD8 T cells involves the availability of new class I major histocompatibility complex (MHC-I)-bound tumor epitopes following therapeutic intervention. Thus, therapy-induced changes within the MHC-I peptidome hold the key to understanding the clinical implications for therapy-reinstated CD8 T cell responses. Here, using mass spectrometry–based immuno-affinity methods and tumor-bearing animals treated with OV and ICB (alone or in combination), we captured the therapy-induced alterations within the tumor MHC-I peptidome, which were then tested for their CD8 T cell response-stimulating activity. We found that the oncolytic reovirus monotherapy drives up- as well as downexpression of tumor MHC-I peptides in a cancer type and oncolysis susceptibility dependent manner. Interestingly, the combination of reovirus + ICB results in higher numbers of differentially expressed MHC-I-associated peptides (DEMHCPs) relative to either monotherapies. Most importantly, OV+ICB-driven DEMHCPs contain biologically active epitopes that stimulate interferon-gamma responses in cognate CD8 T cells, which may mediate clinically desired antitumor attack and cancer immunoediting. These findings highlight that the therapy-induced changes to the MHC-I peptidome contribute toward the reinstated antitumor CD8 T cell attack established following OV + ICB combination cancer immunotherapy.     

Hyaluronan Degradation by Cemip Regulates Host Defense against Staphylococcus aureus Skin Infection

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T-bet+ Memory B Cells Link to Local Cross-Reactive IgG upon Human Rhinovirus Infection

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Do reproductive activities compromise immunological competence as measured by phenoloxidase activity? Field and experimental manipulation in females of two damselfly species

Recent studies of female insects indicate that reproductive activities, such as mating and oviposition, can impair immune ability. Using the two tropical damselfly species Argia anceps Garrison and Hetaerina americana (Fabricius), egg production and phenoloxidase (PO) activity, a key enzyme in insect immunity, are measured in mating, ovipositing and perching females in December and March. Perching females of both species have fewer eggs compared with mating and ovipositing females, which suggests that perching females are not engaged in reproduction. There is seasonal variation in egg number for the three categories in H. americana but not in A. anceps, which can be interpreted in terms of adaptive changes in egg production depending on female–male interactions in the former species but not in the latter species. There is no difference in PO activity among mating, ovipositing or perching females within either species, although measurements in December and March indicate distinct seasonal changes. Juvenile Hormone (JH) is known to reduce the effectiveness of the immune system by favouring the use of resources for reproduction. A possible role for JH is examined in H. americana, using the JH analogue methoprene to manipulate hormone activity, revealing that PO activity is reduced in methoprene‐treated H. americana females. Thus, although the results of the present study are indicative of possible hormone‐driven changes in PO, there is not necessarily a down‐regulation of immune function (as determined by PO activity) during mating or oviposition. The results complement some recent studies countering the idea that reproductive activities reduce the immune ability in insects.     

The Amount of BCL6 in B Cells Shortly after Antigen Engagement Determines Their Representation in Subsequent Germinal Centers

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A Requirement for Argonaute 4 in Mammalian Antiviral Defense

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