Basis Of Innate Immune Response Research Articles

Direct Observation of Repeated Infections With Endemic Coronaviruses.

BackgroundAlthough the mechanisms of adaptive immunity to pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are still unknown, the immune response to the widespread endemic coronaviruses HKU1, 229E, NL63, and OC43 provide a useful reference for understanding repeat infection risk.MethodsHere we used data from proactive sampling carried out in New York City from fall 2016 to spring 2018. We combined weekly nasal swab collection with self-reports of respiratory symptoms from 191 participants to investigate the profile of recurring infections with endemic coronaviruses.ResultsDuring the study, 12 individuals tested positive multiple times for the same coronavirus. We found no significant difference between the probability of testing positive at least once and the probability of a recurrence for the betacoronaviruses HKU1 and OC43 at 34 weeks after enrollment/first infection. We also found no significant association between repeat infections and symptom severity, but found strong association between symptom severity and belonging to the same family.ConclusionsThis study provides evidence that reinfections with the same endemic coronavirus are not atypical in a time window shorter than 1 year and that the genetic basis of innate immune response may be a greater determinant of infection severity than immune memory acquired after a previous infection.

Immune responses to alum in the Japanese pufferfish (Takifugu rubripes)

To elucidate the basis of innate immune responses against insoluble compounds (such as silica and alum) through the inflammasome activation pathway in fish, biological assays and expression analysis of immune-related genes were conducted in the Japanese pufferfish (Takifugu rubripes) head kidney (HK) cells. At first, the Japanese pufferfish was stimulated by intraperitoneal injection of alum (4 mg/fish). After 0, 6, 12, 24 and 48 h post-injection, HK cells were prepared from the injected fish. To understand functionality of activated inflammatory response, phagocytic activity and superoxide anion production (NBT assay) in the HK cells were assessed. As results, the phagocytic and NBT reduction activities were significantly increased in alum-stimulation. To further clarify the immune response through transcriptomic analysis, expression of 19 cytokine genes was checked by the multiplex reverse transcription (RT)-PCR method. Results showed that expression of IL-6 and type I-IFN genes was significantly elevated in the alum-stimulated fish. Furthermore, expression of NLR-C9 and NLR-C12 genes [i.e., NOD-like receptor (NLR) family genes as sensor molecules of inflammasome], ASC and caspase-1 genes (inflammasome associated molecules) were examined by qPCR. Results indicated an increased expression of four different inflammasome associated genes in the HK cells of fish injected with alum. The results suggested activation of inflammatory response to the alum with a likely involvement of inflammasome components in the Japanese pufferfish.

Characterizing the genetic basis of innate immune response in TLR4-activated human monocytes.

Toll-like receptors (TLRs) play a key role in innate immunity. Apart from their function in host defense, dysregulation in TLR signalling can confer risk to autoimmune diseases, septic shock or cancer. Here we report genetic variants and transcripts that are active only during TLR signalling and contribute to interindividual differences in immune response. Comparing unstimulated versus TLR4-stimulated monocytes reveals 1,471 expression quantitative trait loci (eQTLs) that are unique to TLR4 stimulation. Among these we find functional SNPs for the expression of NEU4, CCL14, CBX3 and IRF5 on TLR4 activation. Furthermore, we show that SNPs conferring risk to primary biliary cirrhosis (PBC), inflammatory bowel disease (IBD) and celiac disease are immune response eQTLs for PDGFB and IL18R1. Thus, PDGFB and IL18R1 represent plausible candidates for studying the pathophysiology of these disorders in the context of TLR4 activation. In summary, this study presents novel insights into the genetic basis of the innate immune response and exemplifies the value of eQTL studies in the context of exogenous cell stimulation.

TLRs and IFNs: critical pieces of the autoimmunity puzzle

Discoveries revealing the molecular basis of innate immune responses, particularly the identification of Toll-like receptors (TLRs) as the major recognition sensors for microbial and even self-molecules, have provided new insights into the pathogenesis of both systemic and organ-specific autoimmune diseases. These insights will permit the development of novel treatment modalities for these disorders.

Molecular mechanisms of innate immunity.

All species require a rapid, systemic reply to pathogens in their environment. This response is known as the innate immune response and is characterized by de novo synthesis of mediators that directly or indirectly through phagocytosis remove and kill the pathogen. Innate immune responses have been preserved throughout evolution and have been studied in detail in organisms from the fruit fly Drosophila melanogaster to humans. In my laboratory, studies performed during the past 25 yr have focused on defining the molecular basis of innate immune responses to microbial pathogens. Specifically, we have used bacterial endotoxin (lipopolysaccharide) as a model stimulus to define how the innate immune system recognizes products of microbial pathogens and initiates responses to remove and/or kill such organisms. Such studies also serve as models to understand more fully the mechanisms underlying a serious human disease known as septic shock. This article discusses septic shock and its relationship to innate immunity.