Science
15 August 2008
p917
We know that biting insects transmits viral, bacterial, and parasitic infections. We do not know the initial events that occur as pathogens are introduced by these vectors into the wounds. It is under investigation that early events in vector mediated injury influence the outcome of sandfly-transmitted parasite
Leishmania major.
Neutrophils are the first wave of inflammatory cells that migrate into these sites. They have phagocytic actions are regarded as foot solders armed with oxygen radicals, lytic enzymes, and cationic proteins. Unfortunetly, they are short lived. Their corpes are phagocytosed by macrophages. L. major internalizes by entering neurophils and become phagocytosed.
This was possible with transgenic mice with fluorescent neutrophils and deep tissue immaging.
Was the phagocytic events independent of sand fly bite and L. major internalization? Yes, because they discovered that by injecting beads, a similar accumulation event of neutrophils occured.
Does any interfere with neutrophils accumulate? Tissue damage was proposed as an alternative that overrid the effect of sandfly bite. But sustained recruitment was observed compared with less from just a needle stick.
Most cells that contained L. major were neutrophils after 18 hours. (So there was a time dependance)
and soon after most cells that had L. major were macrophages in 6 to seven days.
What was unexpected was that instead of engulfing dying infected neutrophils, macrophages acquired the parasites that had been released from neutrophils undergoing apoptosis.
BUT, macrophages were not predominant, others were: interleukin-1. Since there was an absence of neutrophils, it hindered the ability to infect macrophages.
An alternative mechanism is that parasites are better adapted to survive in macrophages. (?)
Dendritic cells and Langerhans cells are important to transport the parasite to lymph nodes.
Most parasites die in the neutrophil by oxidative burst.
The Trojan Horse theory is also applicable to Ehrlichia and Francisella tularensis.
Beena John and Christopher A. Hunter
University of Pennsylvania Vet Med
What I Learned
Infections can have a model of entry
The Trojan Horse Theory - Immune cells can care infection
Because something happens (neutrophil recruitment) it might not lead to the next step (macrophage recruitment). Paradoxically, it leads to other recruitment but a less infection.
Just because something should do something (phagocytose) it might not.
What are the Questions I Learned
Every Step needs another explaination. Neutrophils accumlate at wound site, infection or not.
What interfers with accumlation? Possible tissue damage.
What are the things that can hinder the steps?
