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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

Neutrophils are required for the control of O. anthropi infections.(A) Neutrophils were depleted from twenty mice by injection of the anti-neutrophil RB6 antibody and ten additional mice were instead injected with PBS alone. One group of ten mice anti-neutrophil treated and the group of ten mice injected with PBS alone were then infected intraperitoneally with 109 CFU/mouse of O. anthropi. The last group of ten mice treated with antibody anti-neutrophil was inoculated with PBS alone. The lethality of the bacteria was recorded at the indicated times. (B) O. anthropi was mixed with purified rat neutrophils at a ratio of 5±4 bacteria/cell. Control bacteria were not incubated with neutrophils. At the indicated times the viable CFU were determined and the percentage of bacterial replication was calculated. In “B” Values of p<0.01 (*) and p<0.001 (**) are indicated.
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pone-0005893-g004: Neutrophils are required for the control of O. anthropi infections.(A) Neutrophils were depleted from twenty mice by injection of the anti-neutrophil RB6 antibody and ten additional mice were instead injected with PBS alone. One group of ten mice anti-neutrophil treated and the group of ten mice injected with PBS alone were then infected intraperitoneally with 109 CFU/mouse of O. anthropi. The last group of ten mice treated with antibody anti-neutrophil was inoculated with PBS alone. The lethality of the bacteria was recorded at the indicated times. (B) O. anthropi was mixed with purified rat neutrophils at a ratio of 5±4 bacteria/cell. Control bacteria were not incubated with neutrophils. At the indicated times the viable CFU were determined and the percentage of bacterial replication was calculated. In “B” Values of p<0.01 (*) and p<0.001 (**) are indicated.

Mentions: The above results indicated that O. anthropi induces a cellular response compatible with acute bacterial infections and suggested that neutrophils could play a protective role. In addition, we previously observed that neutrophils do not play a significant role in B. abortus infections in mice [3]. Thus, we evaluated the relevance of these leukocytes in controlling O. anthropi using chronic neutropenic mice. Forty-eight hours after infection, all the neutropenic but none of the non-neutropenic mice were dead (Fig. 4A). The role of neutrophils in controlling O. anthropi was confirmed by the results of ex-vivo experiments with rat neutrophils (Fig. 4B).


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)

Neutrophils are required for the control of O. anthropi infections.(A) Neutrophils were depleted from twenty mice by injection of the anti-neutrophil RB6 antibody and ten additional mice were instead injected with PBS alone. One group of ten mice anti-neutrophil treated and the group of ten mice injected with PBS alone were then infected intraperitoneally with 109 CFU/mouse of O. anthropi. The last group of ten mice treated with antibody anti-neutrophil was inoculated with PBS alone. The lethality of the bacteria was recorded at the indicated times. (B) O. anthropi was mixed with purified rat neutrophils at a ratio of 5±4 bacteria/cell. Control bacteria were not incubated with neutrophils. At the indicated times the viable CFU were determined and the percentage of bacterial replication was calculated. In “B” Values of p<0.01 (*) and p<0.001 (**) are indicated.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2691993&req=5

pone-0005893-g004: Neutrophils are required for the control of O. anthropi infections.(A) Neutrophils were depleted from twenty mice by injection of the anti-neutrophil RB6 antibody and ten additional mice were instead injected with PBS alone. One group of ten mice anti-neutrophil treated and the group of ten mice injected with PBS alone were then infected intraperitoneally with 109 CFU/mouse of O. anthropi. The last group of ten mice treated with antibody anti-neutrophil was inoculated with PBS alone. The lethality of the bacteria was recorded at the indicated times. (B) O. anthropi was mixed with purified rat neutrophils at a ratio of 5±4 bacteria/cell. Control bacteria were not incubated with neutrophils. At the indicated times the viable CFU were determined and the percentage of bacterial replication was calculated. In “B” Values of p<0.01 (*) and p<0.001 (**) are indicated.
Mentions: The above results indicated that O. anthropi induces a cellular response compatible with acute bacterial infections and suggested that neutrophils could play a protective role. In addition, we previously observed that neutrophils do not play a significant role in B. abortus infections in mice [3]. Thus, we evaluated the relevance of these leukocytes in controlling O. anthropi using chronic neutropenic mice. Forty-eight hours after infection, all the neutropenic but none of the non-neutropenic mice were dead (Fig. 4A). The role of neutrophils in controlling O. anthropi was confirmed by the results of ex-vivo experiments with rat neutrophils (Fig. 4B).

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