Host defense mechanisms of cephalopods

Humoral and cellular mechanisms of defense have been described for cephalopods, a relatively advanced group of mollusks. Typical of other mollusks, cephalopod agglutinins are the most documented component of humoral immunity. Lectins, which have agglutinating properties, have been described and characterized from octopuses. Agglutinins from cephalopod hemolymph have also been shown to agglutinate a variety of vertebrate red blood cells, as well as potential bacterial pathogens. Hemocytes are the primary component of cellular immunity. Although the hemocyte role in phagocytosis has been extensively studied in other mollusks, the mechanisms of phagocytosis have not been described extensively for cephalopods. Cephalopod hemocytes have phagocytic capabilities and may function in encapsulation and neutralization of foreign substances; however, the effects of environmental factors and the full extent of phagocytic capabilities of cephalopod hemocytes have not been reported. Hemocytes from cephalopods have a role in wound healing and inflammation which have been reported in detail by several investigators.     

Host factors against plant viruses

Plant virus genome replication and movement is dependent on host resources and factors. However, plants respond to virus infection through several mechanisms, such as autophagy, ubiquitination, mRNA decay and gene silencing, that target viral components. Viral factors work in synchrony with pro-viral host factors during the infection cycle and are targeted by antiviral responses. Accordingly, establishment of virus infection is genetically determined by the availability of the pro-viral factors necessary for genome replication and movement, and by the balance between plant defence and viral suppression of defence responses. Sequential requirement of pro-viral factors and the antagonistic activity of antiviral factors suggest a two-step model to explain plant–virus interactions. At each step of the infection process, host factors with antiviral activity have been identified. Here we review our current understanding of host factors with antiviral activity against plant viruses.     

Host defense peptides in wound healing

Host defense peptides are effector molecules of the innate immune system. They show broad antimicrobial action against gram-positive and -negative bacteria, and they likely play a key role in activating and mediating the innate as well as adaptive immune response in infection and inflammation. These features make them of high interest for wound healing research. Non-healing and infected wounds are a major problem in patient care and health care spending. Increasing infection rates, growing bacterial resistance to common antibiotics, and the lack of effective therapeutic options for the treatment of problematic wounds emphasize the need for new approaches in therapy and pathophysiologic understanding. This review focuses on the current knowledge of host defense peptides affecting wound healing and infection. We discuss the current data and highlight the potential future developments in this field of research.     

Host defense effector molecules in mucosal secretions

Mucosal secretions contain a range of defense effector molecules including antimicrobial peptides and proteinase inhibitors. These molecules play a central role in host defense against infection, and in a variety of immune and inflammatory reactions. The aim of this study was to analyze the levels of neutrophil defensins, the cathelicidin hCAP-18/LL-37, and the proteinase inhibitors secretory leukocyte proteinase inhibitor, SKALP/elafin and cystatin M/E in various mucosal secretions and urine. We show here that especially seminal plasma is characterized by high concentrations of hCAP-18/LL-37, SLPI, SKALP/elafin and cystatin M/E. The results of this study demonstrate that each mucosal secretion is characterized by a unique profile of effector molecules, which may supply individual mucosal secretions with specific properties related to the control of local infection and inflammation.     

Host defense deficiency in newborn nonhuman primate lungs

We have investigated two major aspects of the pulmonary host defense mechanism--alveolar macrophage function as a "first line of bacterial defense" and induced neutrophil migration into the lung as a "back-up defense." Chemotactic and phagocytic/killing assays revealed a functional deficiency in the alveolar macrophages of newborn primates. Serial bronchoalveolar lavage investigations revealed diminished neutrophil migration into the newborn primate lung. The overall pulmonary host defense capability in newborn primates was deficient. The results of this investigation may have direct clinical relevance to the susceptibility of newborns to infections and pneumonia.     

Host defense against oropharyngeal and vaginal candidiasis: Site-specific differences

Mucosal candidiasis is extremely common in immunocompromised patients. However, the prevalence of site-specific infection (i.e., oropharyngeal, vaginal, and esophageal candidiasis) can be quite variable depending on the immune status of the host. While vulvovaginal candidiasis is common in normal healthy women, oropharyngeal and esophageal candidiasis are more frequently encountered under immunocompromised states. Candida albicans, the causative agent in most cases of candidiasis, is a commensal organism of the gastrointestinal and lower female reproductive tracts. Thus, most healthy individuals have demonstrable Candida-specific immunity in the peripheral circulation. The pathogenic state is often precipitated by a deficiency or dysfunction in this immunity. Studies from animal models, women with recurrent vulvovaginal candidiasis, and HIV-infected individuals, however, suggest that distinct host defense mechanisms may function against oropharyngeal and vulvovaginal candidiasis. While cell-mediated immunity (CMI) appears important for protection against oropharyngeal candidiasis (OPC), there is little evidence to indicate that T cell-mediated immunity is protective against vulvovaginal candidiasis (VVC). Furthermore, whereas both local and systemically derived immune defenses appear important for protection against OPC, host defenses that protect against VVC appear limited to the local tissue and possibly restricted to innate mechanisms. Thus, current evidence suggests that VVC, unlike OPC, may not represent a strict opportunistic infection.     

Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts

Pseudomonas aeruginosa infection is a serious complication in patients with cystic fibrosis and in immunocompromised individuals. Here we show that P. aeruginosa infection triggers activation of the acid sphingomyelinase and the release of ceramide in sphingolipid-rich rafts. Ceramide reorganizes these rafts into larger signaling platforms that are required to internalize P. aeruginosa, induce apoptosis and regulate the cytokine response in infected cells. Failure to generate ceramide-enriched membrane platforms in infected cells results in an unabated inflammatory response, massive release of interleukin (IL)-1 and septic death of mice. Our findings show that ceramide-enriched membrane platforms are central to the host defense against this potentially lethal pathogen.     

Host defense peptide LL-37 selectively reduces proinflammatory macrophage responses

The human cathelicidin peptide, LL-37, is a host defense peptide with a wide range of immunomodulatory activities and modest direct antimicrobial properties. LL-37 can exert both pro- and anti-inflammatory effects and can modulate the proinflammatory responses of human peripheral blood monocytes and epithelial cells. In this study, we evaluated the effect of LL-37 on mouse bone marrow-derived macrophages (BMDM) and tissue macrophages in vitro and in vivo. LL-37 dramatically reduced TNF-α and NO levels produced by LPS and IFN-γ-polarized M1-BMDM and slightly reduced reactive oxygen species production by these cells. LL-37 did not affect the ability of IL-4-polarized M2-BMDM to upregulate arginase activity, although it did inhibit LPS-induced TNF-α secretion in these cells. LL-37 did not compromise the ability of M1-polarized BMDM to phagocytose and kill bacteria and did not affect the uptake of apoptotic neutrophils by M2-polarized BMDM. However, LL-37-treated M1-BMDM were more efficient at suppressing tumor growth in vitro. LL-37 significantly reduced LPS-induced TNF-α secretion in ex vivo alveolar macrophages, whereas its effect on peritoneal macrophages was much less dramatic. Effective inhibition of LPS-induced TNF-α secretion by alveolar macrophages also occurred in vivo when LL-37 was administered by intratracheal injection. This demonstrates a selective ability of LL-37 to decrease M1-BMDM, M2-BMDM, and tissue macrophage production of the proinflammatory cytokine TNF-α in response to LPS while leaving other crucial anti-inflammatory M1 and M2 macrophage functions unaltered.     

Host defense peptides and the new line of defence against multiresistant infections

Increasing antibiotic resistance has led to an urgent need for new therapeutic approaches. Host defense peptides are known to be antimicrobial and have revealed broad immunomodulatory functions for both innate and adaptive immunity. This review will focus on the role of host defense peptides in infection and immune response and discuss its potential and limitations as a future therapeutical agent.     

Host Susceptibility to endogenous viruses: defective, glycoprotein-expressing proviruses interfere with infections.

Three defective endogenous avian leukosis viruses, ev3, ev6 and ev9, interfered with subgroup E virus infections, ev3, ev6, and ev9 expressed high levels of subgroup E envelope glycoproteins. These glycoproteins reduced the activity of cellular receptors for subgroup E viruses. ev3 and ev6 protected chickens and cultured cells from subgroup E virus infections.