The second issue of the Journal of Innate Immunity in 2018 is another example of the manifold areas covered by the innate immune system. For instance, Irmscher et al. [1] describe a novel mechanism where the plasma enzyme kallikrein cleaves the key complement component C3. The cleavage site is identical to that of C3 convertase, and generated C3b forms C3 convertases, triggering the C3 amplification loop. Ultimately, these events merge with the amplification loop of the alternative pathway. This emphasizes the key importance of complement, with several pathways to cause activation, resulting in the subsequent immune responses including the opsonization of bacteria, the promotion of chemotaxis, phagocytosis, and bacterial killing executed by the neutrophils [2-4].
In the airways, immunity is obviously aimed at keeping us healthy, clearing infections, and promoting healing processes [5-10]. However, long-standing and dysregulated inflammation in the airways is a key feature of several states of disease, e.g., in COPD and cystic fibrosis [11-13]. Furthermore, without a preceding chronic airway inflammation, the host response may cause tissue damage [10, 14]. This may release damage-associated molecular patterns (DAMPs), e.g., extracellular histones, that promote inflammation and aggravate tissue injury [15].
The findings presented in this issue by Ito et al. [16] are highly interesting, showing that Toll-interacting protein (Tollip), a key negative regulator of innate immunity, downregulates IL-13-mediated pulmonary eosinophilia in mice. This points to a potential novel target for dampening inflammation in allergic asthma.
Depriving bacteria of iron with iron-binding proteins or by downregulating access to the iron of the host is an important arm of innate host defense [17]. In their interesting study, Coates et al. [18] show that this is a strategy also utilized by the evolutionarily ancient sea urchin. The sea urchin achieves this via the release of the naphthoquinone pigment echinochrome A from red spherule cells, thereby acting as a primate chelator of iron in the extracellular environment.
Oncolytic viruses are a novel and promising strategy for treating cancer [19]. However, the effects of these viruses on the immune system are not yet fully explored. Tomczyk et al. [20] study the oncolytic vesicular stomatitis virus (VSV), which can be delivered intravenously to target primary and metastatic lesions. They show that VSV infection triggers the differentiation of blood monocytes into immature dendritic cells as well as their apoptosis, the effects of which can have profound immunological consequences and so need to be elucidated further.
Invasive aspergillosis is a major clinical challenge in immunocompromised patients. It is commonly caused by Aspergillus fumigatus whereas A. nidulans is seldom seen; however, in patients suffering from chronic granulomatous disease patients, A. nidulans is a frequent cause of invasive aspergillosis. Thus, interactions with the human host defense likely differ between these 2 pathogens [21]. Gresnigt et al. [22] present a study where they show that A. nidulans induced a lower oxidative burst but a higher production of cytokines in peripheral blood mononuclear cells. This resulted in a slower rate of killing in the case of A. nidulans when compared to A. fumigatus, demonstrating differences with respect to immune system interactions that can explain selective advantages during the infection of compromised hosts.
Taken together, this issue of the Journal of Innate Immunity presents a broad set of perspectives on innate immunity that we hope makes for enjoyable reading!
Heiko Herwald, Lund
Arne Egesten, Lund
