Posted by Kasra Hassani
I am appointed to do a review paper for a ‘Reading and Conference’ course on Fungi. I chose the opportunistic pathogen Aspergillus fumigatus as the focus of my review. Having studied only on Trypanosomes and innate immune cells so far, my background in mycology is close to zero. So I decided to start from scratch. I stepped upon a surprisingly neatly written review that gave me exactly as much background I needed on Aspergillus before I would go more in depth on the subject. “Aspergillus: A primer for the novice” by Dr. Joan Bennett includes scientifically exciting and still critical detail about various species of Aspergillus, their commercial, historical and culinary(yes!) importance. For once after a long time I read the whole review paper and not only the section that interested my research focus. If interested to learn more about the ubiquitous fungus Aspergillus, you can also enjoy reading this paper alongside your favorite afternoon beverage here.
Bennett JW (2009). Aspergillus: a primer for the novice. Medical mycology : official publication of the International Society for Human and Animal Mycology, 47 Suppl 1 PMID: 19253144
Posted by: Kasra Hassani
Many pathogens are unable to live outside the host. Therefore, before killing or completely using up their host, they should ensure that they will be successfully transfered to another one, or one may say, those who did not never made it through evolution. Depending on their life-cycle and type, strategies to ensure transmission diffes among pathogens. In a comment for Nature Reviews in Immunology Sacks and Yazdanbakhsh comparatively discuss these strategies among air-borne pathogens, protozoan vector borne pathogens and also multicellular pathogens. Air-borne bacteria and viruses can easily spread after an acute infection and do not necessarily need to modulate immune response to avoid the up-coming sterilizing immunity. On the other hand, vector-borne parasites such as Plasmodium or the Trypanosomes require more time for efficient transmission. Therefore, parasites have developed strategies to delay life-long immunity. For instance, in African Trypanosomes (T. brucei) continuous variation of the surface glycoprotein (correctly named the variable surface glycoprotein or VSG) hiders development of a protective immune response and allows the parasite to reside in the blood for a long time. Alternatively, Leishmania infections co-inside with presence of regulatory T cells and considerable amounts of IL-10 which down-regulates the protective Th1 response. In larger parasites such as helminths rapid movement from immune-sensitive areas such as the skin or acquiring and presentation of host antigens are among the strategies that are used for delaying the immune response and buying time for transmission.
What I find more interesting among all of this is the evolution of the host in the same direction. In many parasitic infections, the immune response does not lead to complete parasite clearance, rather to a residual infection with minimum or no pathology yet still transmissibility. Read et al. have argued in a Primer in PLoS Biology that this ‘tolerance’ is a type of immunity that can arise in the host-parasite co-evolution as an alternative to ‘resistance’ where complete of the pathogen clearance occurs. Firstly, complete clearance of the pathogen can be too costly compared to its control. Secondly, In the dynamic co-evolution of the host and the parasite, genes who confer tolerance against a pathogen could be favored to those who confer resistance. Evolution of tolerance does not harm or might even favor parasite existence since tolerant host are reservoirs of the parasites within the population. Therefore, they do not prompt counter-adaptation by the parasites.
Sacks and Yazdanbakhsh conclude their comment by mentioning that these immune strategies should be taken into consideration when designing vaccines for parasitic diseases. They suggest that instead of trying to override this desire of the immune system for tolerance rather than resistance, vaccines could induce tolerance where minimal pathology is caused by a controlled persistence of the parasites. A classic example of a vaccination strategy in this line is Leishmanization wherein live Leishmania parasites used to be inoculated in soldiers or children in risk of infection and would confer immunity to further infections. With regard to development of immunological tolerance to leishmaniasis, not resistance, these types of vaccines need reconsideration.
Posted by: Kasra Hassani
I remember some years ago when I used to read about ecology, behavior and evolution, how fascinated I was by the classic book of G. Evelyn Hutchinson, The ecological theater and the evolutionary play (1965) and by the way that book was depicting niches in ecology and evolution. Separation of niches and consequent speciation occurs constantly and could look simple in the first look. On the other hand, the resulting diversity could be also beyond imagination. Different depths in the cork of an old tree in a tropic jungle can provide different micro-environments to the species living in them, both micro and macroscopic. Various tiny species of insects and other invertebrates could live in different depths of the cork of the tree; different species of birds could feed from them using specialized beaks that penetrate different depths of the cork, so that they would not enter the other species’ niche. It does not just end there. Species distribution varies by height of the tree as so do the mico-environments. And yet even more, in some cases speciation can be temporal with different species of birds coming to the tree at different times during the day. Thus, a tree could act as countless niches for countless species and thus countless biologic diversity.
Years later, I stumbled upon the same phenomenon in the world of parasites. As I was looking through the second chapter of “Foundations of Parasitology” by Schmidt and Roberts (2005), I realized that the vertebrate intestinal tract could be looked at the same way as a tree. Along the intestinal tract, different environments exist, in terms of physical conditions, nutrients, pH and enzymes. Therefore, we should not be surprised to see the same trend and observe different parasites adapting to different micro-environments along the tract and staying away from each other. Below is a graph of distribution of different intestinal worms along the intestine tract of a bird. The bar shows distance from the stomach. Specialization and separation of niches among different parasites can be readily seen (Stock and Holmes 1988).
Another study that the book chapter mentions is about 8 different species of nematodes that were found to be distributed in the intestine of a turtle, not only longitudinally but also radially with preferences towards either lumen or the ring of the intestine (Schad, 1965).
Sometimes we go in so deep into our molecules that we miss the big picture of biology of parasites. How they interact with each other and with their hosts in an ecological and evolutionary point of view. I guess the beauty of biology is that no matter how diverse and complicated the organisms and their relationships can get, still the same principles and patterns apply.
Identification of Key Cytosolic Kinases Containing Evolutionarily Conserved Kinase Tyrosine-based Inhibitory Motifs (KTIMs).
Posted by: Issa Abu-Dayyeh
I have posted an earlier article to talk about our PLoS NTD paper where we have described a novel strategy by which Leishmania was able to inhibit TLR-mediated macrophage activation through its ability to inhibit IRAK-1 kinase activity by activating the protein tyrosine phosphatase (PTP) SHP-1.
We have identified the site of binding between SHP-1 and IRAK-1 to be an evolutionarily conserved ITIM-like motif, which we called a kinase tyrosine-based inhibitory motif (KTIM). In this newly-published paper in Developmental and Comparative Immunology, Abu-Dayyeh et al. present evolutinary as well as experimental data that propose that KTIMs could potentially represent a novel regulatory site involved in the control of the kinase activity of many key kinases involved in siganlling pathways of immune cells. Although this work awaits to be further explored by other researches, I believe this work could open various doors towards many important discoveries in the field of immunology.
Here is the abstract of the paper:
We previously reported that SHP-1 regulates IRAK-1 activity by binding to an ITIM-like motif found within its kinase domain, which we named Kinase Tyrosine-based Inhibitory Motif (KTIM). Herein, we further investigated the presence, number, location, and evolutionary time of emergence of potential KTIMs in many cytosolic kinases, all known to play important roles in the signalling and function of immune cells. We unveil that several kinases contain potential KTIMs, mostly located within their kinase domain and appearing predominantly at the level of early vertebrates becoming highly conserved thereafter. Regarding the KTIMs that were found conserved in both vertebrates and invertebrates, we provide experimental data suggesting that such motifs may have constituted readily-available sites that performed new regulatory functions as soon as their binding partners (e.g. SHP-1) appeared in vertebrates. We thus propose KTIMs as novel regulatory motifs in kinases that function through binding to SH2 domain-containing proteins such as SHP-1. Copyright © 2009. Published by Elsevier Ltd.