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The differential interaction of Brucella and ochrobactrum with innate immunity reveals traits related to the evolution of stealthy pathogens.

Barquero-Calvo E, Conde-Alvarez R, Chacón-Díaz C, Quesada-Lobo L, Martirosyan A, Guzmán-Verri C, Iriarte M, Mancek-Keber M, Jerala R, Gorvel JP, Moriyón I, Moreno E, Chaves-Olarte E - PLoS ONE (2009)

Bottom Line: During evolution, innate immunity has been tuned to recognize pathogen-associated molecular patterns.The results suggest that Brucellaceae ancestors carried molecules not readily recognized by innate immunity, so that non-drastic variations led to the emergence of stealthy intracellular parasites.They also suggest that some critical envelope properties, like selective permeability, are profoundly altered upon modification of pathogen-associated molecular patterns, and that this represents a further adaptation to the host.

View Article: PubMed Central - PubMed

Affiliation: Programa de Investigación en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional, Heredia, Costa Rica.

ABSTRACT

Background: During evolution, innate immunity has been tuned to recognize pathogen-associated molecular patterns. However, some alpha-Proteobacteria are stealthy intracellular pathogens not readily detected by this system. Brucella members follow this strategy and are highly virulent, but other Brucellaceae like Ochrobactrum are rhizosphere inhabitants and only opportunistic pathogens. To gain insight into the emergence of the stealthy strategy, we compared these two phylogenetically close but biologically divergent bacteria.

Methodology/principal findings: In contrast to Brucella abortus, Ochrobactrum anthropi did not replicate within professional and non-professional phagocytes and, whereas neutrophils had a limited action on B. abortus, they were essential to control O. anthropi infections. O. anthropi triggered proinflammatory responses markedly lower than Salmonella enterica but higher than B. abortus. In macrophages and dendritic cells, the corresponding lipopolysaccharides reproduced these grades of activation, and binding of O. anthropi lipopolysaccharide to the TLR4 co-receptor MD-2 and NF-kappaB induction laid between those of B. abortus and enteric bacteria lipopolysaccharides. These differences correlate with reported variations in lipopolysaccharide core sugars, sensitivity to bactericidal peptides and outer membrane permeability.

Conclusions/significance: The results suggest that Brucellaceae ancestors carried molecules not readily recognized by innate immunity, so that non-drastic variations led to the emergence of stealthy intracellular parasites. They also suggest that some critical envelope properties, like selective permeability, are profoundly altered upon modification of pathogen-associated molecular patterns, and that this represents a further adaptation to the host. It is proposed that this adaptive trend is relevant in other intracellular alpha-Proteobacteria like Bartonella, Rickettsia, Anaplasma, Ehrlichia and Wolbachia.

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Related in: MedlinePlus

OaLPS induces dendritic cell maturation that lay between BaLPS. and SeLPS.(A) BMDC were incubated with 0.1 µg of EcLPS, 10 µg of BaLPS or 10 µg of OaLPS in 1 ml culture and labeled with the anti-FK2 antibody for detection of DALIS at 24 h. The percentage of BMDC positive for DALIS is indicated. (B) BMDC incubated as in “A” were labeled with fluorescent anti-CD40, CD-80, CD-86 and MHC II. Values of median fluorescence correspond to four independent experiments. Values of p< 0.05 (*) and p<0.005 (**) with respect to BaLPS are indicated.
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pone-0005893-g008: OaLPS induces dendritic cell maturation that lay between BaLPS. and SeLPS.(A) BMDC were incubated with 0.1 µg of EcLPS, 10 µg of BaLPS or 10 µg of OaLPS in 1 ml culture and labeled with the anti-FK2 antibody for detection of DALIS at 24 h. The percentage of BMDC positive for DALIS is indicated. (B) BMDC incubated as in “A” were labeled with fluorescent anti-CD40, CD-80, CD-86 and MHC II. Values of median fluorescence correspond to four independent experiments. Values of p< 0.05 (*) and p<0.005 (**) with respect to BaLPS are indicated.

Mentions: Dendritic cells are key elements linking innate and adaptive immunity. Since the evidence presented above situates the induction of innate immunity by O. anthropi between those elicited by enteric bacteria and B. abortus, we wanted to know whether this was also true in these cells. To this purpose, we measured the ability of the respective LPSs to trigger the formation of the dendritic cell aggregosome-like induced structures (DALIS) characteristic of the maturation of these cells. As expected, EcLPS induced more DALIS than BaLPS. Moreover, in keeping with all the above-described results, OaLPS displayed an activity that lay between BaLPS and EcLPS (Fig. 8A). To confirm this, we measured the expression of maturation markers in LPS-treated dendritic cells. As compared to BaLPS, OaLPS induced a significantly higher expression of surface CD40, CD80, CD86 and MHC-II which was, however, lower than that triggered by EcLPS (Fig. 8B).


The differential interaction of Brucella and ochrobactrum with innate immunity reveals traits related to the evolution of stealthy pathogens.

Barquero-Calvo E, Conde-Alvarez R, Chacón-Díaz C, Quesada-Lobo L, Martirosyan A, Guzmán-Verri C, Iriarte M, Mancek-Keber M, Jerala R, Gorvel JP, Moriyón I, Moreno E, Chaves-Olarte E - PLoS ONE (2009)

OaLPS induces dendritic cell maturation that lay between BaLPS. and SeLPS.(A) BMDC were incubated with 0.1 µg of EcLPS, 10 µg of BaLPS or 10 µg of OaLPS in 1 ml culture and labeled with the anti-FK2 antibody for detection of DALIS at 24 h. The percentage of BMDC positive for DALIS is indicated. (B) BMDC incubated as in “A” were labeled with fluorescent anti-CD40, CD-80, CD-86 and MHC II. Values of median fluorescence correspond to four independent experiments. Values of p< 0.05 (*) and p<0.005 (**) with respect to BaLPS are indicated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2691993&req=5

pone-0005893-g008: OaLPS induces dendritic cell maturation that lay between BaLPS. and SeLPS.(A) BMDC were incubated with 0.1 µg of EcLPS, 10 µg of BaLPS or 10 µg of OaLPS in 1 ml culture and labeled with the anti-FK2 antibody for detection of DALIS at 24 h. The percentage of BMDC positive for DALIS is indicated. (B) BMDC incubated as in “A” were labeled with fluorescent anti-CD40, CD-80, CD-86 and MHC II. Values of median fluorescence correspond to four independent experiments. Values of p< 0.05 (*) and p<0.005 (**) with respect to BaLPS are indicated.
Mentions: Dendritic cells are key elements linking innate and adaptive immunity. Since the evidence presented above situates the induction of innate immunity by O. anthropi between those elicited by enteric bacteria and B. abortus, we wanted to know whether this was also true in these cells. To this purpose, we measured the ability of the respective LPSs to trigger the formation of the dendritic cell aggregosome-like induced structures (DALIS) characteristic of the maturation of these cells. As expected, EcLPS induced more DALIS than BaLPS. Moreover, in keeping with all the above-described results, OaLPS displayed an activity that lay between BaLPS and EcLPS (Fig. 8A). To confirm this, we measured the expression of maturation markers in LPS-treated dendritic cells. As compared to BaLPS, OaLPS induced a significantly higher expression of surface CD40, CD80, CD86 and MHC-II which was, however, lower than that triggered by EcLPS (Fig. 8B).

Bottom Line: During evolution, innate immunity has been tuned to recognize pathogen-associated molecular patterns.The results suggest that Brucellaceae ancestors carried molecules not readily recognized by innate immunity, so that non-drastic variations led to the emergence of stealthy intracellular parasites.They also suggest that some critical envelope properties, like selective permeability, are profoundly altered upon modification of pathogen-associated molecular patterns, and that this represents a further adaptation to the host.

View Article: PubMed Central - PubMed

Affiliation: Programa de Investigación en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional, Heredia, Costa Rica.

ABSTRACT

Background: During evolution, innate immunity has been tuned to recognize pathogen-associated molecular patterns. However, some alpha-Proteobacteria are stealthy intracellular pathogens not readily detected by this system. Brucella members follow this strategy and are highly virulent, but other Brucellaceae like Ochrobactrum are rhizosphere inhabitants and only opportunistic pathogens. To gain insight into the emergence of the stealthy strategy, we compared these two phylogenetically close but biologically divergent bacteria.

Methodology/principal findings: In contrast to Brucella abortus, Ochrobactrum anthropi did not replicate within professional and non-professional phagocytes and, whereas neutrophils had a limited action on B. abortus, they were essential to control O. anthropi infections. O. anthropi triggered proinflammatory responses markedly lower than Salmonella enterica but higher than B. abortus. In macrophages and dendritic cells, the corresponding lipopolysaccharides reproduced these grades of activation, and binding of O. anthropi lipopolysaccharide to the TLR4 co-receptor MD-2 and NF-kappaB induction laid between those of B. abortus and enteric bacteria lipopolysaccharides. These differences correlate with reported variations in lipopolysaccharide core sugars, sensitivity to bactericidal peptides and outer membrane permeability.

Conclusions/significance: The results suggest that Brucellaceae ancestors carried molecules not readily recognized by innate immunity, so that non-drastic variations led to the emergence of stealthy intracellular parasites. They also suggest that some critical envelope properties, like selective permeability, are profoundly altered upon modification of pathogen-associated molecular patterns, and that this represents a further adaptation to the host. It is proposed that this adaptive trend is relevant in other intracellular alpha-Proteobacteria like Bartonella, Rickettsia, Anaplasma, Ehrlichia and Wolbachia.

Show MeSH
Related in: MedlinePlus