Sculpting the immune response to infection

Centre for Innate Immunity and Infectious Diseases, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia.
Nature Immunology (Impact Factor: 20). 06/2011; 12(7):579-82. DOI: 10.1038/ni0711-579
Source: PubMed


This report describes advances in the understanding of how microbes elicit and evade immune responses and the sensing of pathogens by host cells that leads to the activation and production of intra- and extracellular signaling molecules.

Download full-text


Available from: Paul J Hertzog
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Interferons (IFNs) comprise type I, II and III families with multiple subtypes. Via transcription of IFN-stimulated genes (ISGs), IFNs can exert multiple biological effects on the cell. In infectious and chronic inflammatory diseases, the IFNs and their ISG sets can be potentially utilized as biomarkers of disease outcome. Animal models allow investigations into disease pathogenesis and gene knockout models have proved cause and effect relationships of molecules related to the IFN response. Sets of IFN subtypes and their ISG products provide immunological signature patterns for different viral and other diseases. In this article, we give an overview of IFNs in several virus infection models and autoimmune diseases of medical relevance. Lessons learned from animal models inform us of IFN system parameters as indicators of disease outcome and whether clinical research is warranted. Moreover, validated IFN biomarkers for prognosis enhance our understanding of therapeutic and vaccine development.
    Full-text · Article · Apr 2012 · Biomarkers in Medicine
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Columnaris disease, caused by the bacterial pathogen Flavobacterium columnare, continues to be a major problem worldwide and commonly leads to tremendous losses of both wild and cultured freshwater fish, particularly in intensively farmed aquaculture species such as channel catfish. Despite its ecologic and economic impacts, the fundamental molecular mechanisms of the host immune response to this pathogen remain unclear. While F. columnare can induce marked pathologic changes in numerous ectopic tissues, the adhesion of F. columnare to the gill in particular is strongly associated with pathogen virulence and host susceptibility. Recently, in this regard, using RNA-seq expression profiling we found that a rhamnose-binding lectin (RBL) was dramatically upregulated in the gill of fish infected with F. columnare (as compared to naïve fish). Thus, in the present study we sought to further characterize and understand the RBL response in channel catfish (Ictalurus punctatus). We first identified two distinct catfish families with differential susceptibilities to columnaris disease; one family was found to be completely resistant while the other was susceptible (0% mortality versus 18.3% respectively, P < 0.001). Exclusively, in the susceptible family, we observed an acute and robust upregulation in catfish RBL that persisted for at least 24 h (P < 0.05). To elucidate whether RBL play a more direct role in columnaris pathogenesis, we exposed channel catfish to different doses of the putative RBL ligands l-rhamnose and d-galactose, and found that these sugars, protected channel catfish against columnaris disease, likely through competition with F. columnare binding of host RBL. Finally, we examined the role of nutritional status on RBL regulation and found that RBL expression was upregulated (>120-fold; P < 0.05) in fish fasted for 7 d (as compared to fish fed to satiation daily), yet expression levels returned to those of satiated fish within 4 h after re-feeding. Collectively, these findings highlight putative roles for RBL in the context of columnaris disease and reveal new aspects linking RBL regulation to feed availability.
    Full-text · Article · Aug 2012 · Fish & Shellfish Immunology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The mucosal surfaces of fish serve as the first line of defense against the myriad of aquatic pathogens present in the aquatic environment. The immune repertoire functioning at these interfaces is still poorly understood. The skin, in particular, must process signals from several fronts, sensing and integrating environmental, nutritional, social, and health cues. Pathogen invasion can disrupt this delicate homeostasis with profound impacts on signaling throughout the organism. Here, we investigated the transcriptional effects of virulent Aeromonas hydrophila infection in channel catfish skin, Ictalurus punctatus. We utilized a new 8 x 60K Agilent microarray for catfish to examine gene expression profiles at critical early timepoints following challenge-2 h, 8 h, and 12 h. Expression of a total of 2,168 unique genes was significantly perturbed during at least one timepoint. We observed dysregulation of genes involved in antioxidant, cytoskeletal, immune, junctional, and nervous system pathways. In particular, A. hydrophila infection rapidly altered a number of potentially critical lectins, chemokines, interleukins, and other mucosal factors in a manner predicted to enhance its ability to adhere to and invade the catfish host.
    Full-text · Article · Dec 2012 · Developmental and comparative immunology
Show more