Limits...
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.

Show MeSH

Related in: MedlinePlus

O. anthropi induces TNF-α that lays between B. abortus and S. enterica.(A) Murine Raw 264.7 macrophages were infected for 30 min with O. anthropi or B. abortus at a MOI of 500. Extracellular bacteria were killed by addition of gentamicin. At the indicated times samples from the culture media were taken and processed for TNF-α quantification. (B) Groups of 6 mice were inoculated intraperitoneally with O. anthropi. At the indicated times mice were bled and TNF-α levels were determined. The levels of TNF-α induction after 3 h of an equivalent inoculation of B. abortus or S. enterica. Value of p<0.001 (**) is indicated.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2691993&req=5

pone-0005893-g006: O. anthropi induces TNF-α that lays between B. abortus and S. enterica.(A) Murine Raw 264.7 macrophages were infected for 30 min with O. anthropi or B. abortus at a MOI of 500. Extracellular bacteria were killed by addition of gentamicin. At the indicated times samples from the culture media were taken and processed for TNF-α quantification. (B) Groups of 6 mice were inoculated intraperitoneally with O. anthropi. At the indicated times mice were bled and TNF-α levels were determined. The levels of TNF-α induction after 3 h of an equivalent inoculation of B. abortus or S. enterica. Value of p<0.001 (**) is indicated.

Mentions: Proinflammatory cytokines, particularly TNF-α, increase during acute Gram negative infections but not at the onset of brucellosis. When we studied this in comparative terms, we found that murine macrophages infected with O. anthropi released significantly higher amounts of TNF-α than cells infected with B. abortus (Fig. 6A), and this observation held true in vivo since mice displayed higher TNF-α blood levels when inoculated with O. anthropi than with B. abortus (Fig. 6B). O. anthropi, however, was not as efficient as S. enterica in the induction of TNF-α release in vivo (Fig. 6B).


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)

O. anthropi induces TNF-α that lays between B. abortus and S. enterica.(A) Murine Raw 264.7 macrophages were infected for 30 min with O. anthropi or B. abortus at a MOI of 500. Extracellular bacteria were killed by addition of gentamicin. At the indicated times samples from the culture media were taken and processed for TNF-α quantification. (B) Groups of 6 mice were inoculated intraperitoneally with O. anthropi. At the indicated times mice were bled and TNF-α levels were determined. The levels of TNF-α induction after 3 h of an equivalent inoculation of B. abortus or S. enterica. Value of p<0.001 (**) is indicated.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0005893-g006: O. anthropi induces TNF-α that lays between B. abortus and S. enterica.(A) Murine Raw 264.7 macrophages were infected for 30 min with O. anthropi or B. abortus at a MOI of 500. Extracellular bacteria were killed by addition of gentamicin. At the indicated times samples from the culture media were taken and processed for TNF-α quantification. (B) Groups of 6 mice were inoculated intraperitoneally with O. anthropi. At the indicated times mice were bled and TNF-α levels were determined. The levels of TNF-α induction after 3 h of an equivalent inoculation of B. abortus or S. enterica. Value of p<0.001 (**) is indicated.
Mentions: Proinflammatory cytokines, particularly TNF-α, increase during acute Gram negative infections but not at the onset of brucellosis. When we studied this in comparative terms, we found that murine macrophages infected with O. anthropi released significantly higher amounts of TNF-α than cells infected with B. abortus (Fig. 6A), and this observation held true in vivo since mice displayed higher TNF-α blood levels when inoculated with O. anthropi than with B. abortus (Fig. 6B). O. anthropi, however, was not as efficient as S. enterica in the induction of TNF-α release in vivo (Fig. 6B).

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