AUTHOR=Gomes Thiago Santos , Gjiknuri Julia , Magnet Angela , Vaccaro Lucianna , Ollero Dolores , Izquierdo Fernando , Fenoy Soledad , Hurtado Carolina , del Águila Carmen 

TITLE=The Influence of Acanthamoeba–Legionella Interaction in the Virulence of Two Different Legionella Species

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.02962

DOI=10.3389/fmicb.2018.02962

ISSN=1664-302X

ABSTRACT=<p>The genus <italic>Legionella</italic> comprises more than 60 species, and about half are associated with infection. <italic>Legionella pneumophila</italic> is the most commonly associated with these infections and by far the most studied, but <italic>L.</italic> non-<italic>pneumophila</italic> species, such as <italic>L. feeleii</italic>, <italic>L. anisa</italic>, etc., may also present clinical importance. Free-living amoebae are their preferred environmental host, where these bacteria not only survive but also succeed in multiplying, and this relationship can lead to an increase in bacterial virulence. The goal of this study was to evaluate the alterations of <italic>Legionella</italic> pathogenicity due to its interaction with <italic>Acanthamoeba</italic>. For this, the expression of protein effectors SdhA, LegK2, and SidK were evaluated in <italic>L. pneumophila</italic> and <italic>L. feeleii</italic>, before and after infecting <italic>Acanthamoeba</italic>. Additionally, the host response was evaluated by measuring the production of IL-6, IL-8, and IFN-γ in infected macrophages. Regarding the virulence factors, an increase in SdhA expression was observed after these bacteria infected <italic>Acanthamoeba</italic>, with a higher increase in the macrophage cultures infected with <italic>L. feeleii</italic>. Also, an increase in the expression of LegK2 was observed after infecting <italic>Acanthamoeba</italic>, but it was more intense in the cultures infected with <italic>L. pneumophila</italic>. With regard to SidK, it was increased in <italic>L. feeleii</italic> after infecting <italic>Acanthamoeba</italic>, however the same effect was not observed for <italic>L. pneumophila</italic>. In cytokine production, the effect on IL-6 and IL-8 was similar for both cytokines, increasing their concentration, but higher production was observed in the cultures infected with <italic>L. feeleii</italic>, even though it demonstrated slightly lower production with the inoculum obtained from <italic>Acanthamoeba</italic>. Concerning IFN-γ, induction was observed in both species but higher in the infection by <italic>L. pneumophila</italic>. Nevertheless, it is not known if this induction is enough to promote an efficient immune response against either <italic>L. pneumophila</italic> or <italic>L. feeleii</italic>. Altogether, these alterations seem to increase <italic>L. feeleii</italic> virulence after infecting <italic>Acanthamoeba</italic>. However, this increase does not seem to turn <italic>L. feeleii</italic> as virulent as <italic>L. pneumophila</italic>. More studies are necessary to understand the aspects influenced in these bacteria by their interaction with <italic>Acanthamoeba</italic> and, thus, identify targets to be used in future therapeutic approaches.</p>