Limits...
Attenuated response of aged mice to respiratory Francisella novicida is characterized by reduced cell death and absence of subsequent hypercytokinemia.

Mares CA, Sharma J, Ojeda SS, Li Q, Campos JA, Morris EG, Coalson JJ, Teale JM - PLoS ONE (2010)

Bottom Line: Age associated attenuations of various immune parameters, involved with both innate and adaptive responses are collectively known as immune senescence.These changes are likely to be involved with differences in host susceptibility to disease between young and aged individuals.In addition, the small cohort of aged survivors did not progress to a severe sepsis syndrome with hypercytokinemia, as did all of the young adult mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.

ABSTRACT

Background: Pneumonia and pulmonary infections are major causes of mortality among the growing elderly population. Age associated attenuations of various immune parameters, involved with both innate and adaptive responses are collectively known as immune senescence. These changes are likely to be involved with differences in host susceptibility to disease between young and aged individuals.

Methodology/principal findings: The objective of this study was to assess potential age related differences in the pulmonary host response in mice to the Gram-negative respiratory pathogen, Francisella novicida. We intranasally infected mice with F. novicida and compared various immune and pathological parameters of the pulmonary host response in both young and aged mice.

Conclusions/significance: We observed that 20% of aged mice were able to survive an intranasal challenge with F. novicida while all of their younger cohorts died consistently within 4 to 6 days post infection. Further experiments revealed that all of the aged mice tested were initially able to control bacterial replication in the lungs as well as at distal sites of replication compared with young mice. In addition, the small cohort of aged survivors did not progress to a severe sepsis syndrome with hypercytokinemia, as did all of the young adult mice. Finally, a lack of widespread cell death in potential aged survivors coupled with a difference in cell types recruited to sites of infection within the lung confirmed an altered host response to Francisella in aged mice.

Show MeSH

Related in: MedlinePlus

Aged mice display an altered pulmonary pathology in response to F. novicda.Young and aged mice were intransally infected with F. novicida. Lungs were harvested at various time points and H&E staining was performed to help assess the pathology associated with the course of infection. Panels A and D show mock lungs from young and aged mice, respectively. The arrow indicates perivascular mononuclear cells present in mock aged lung. Panels B and E depict the lungs of young and aged mice at 3 DPI. The asterisk is highlighting large foci of necrosis that is typical by 3 DPI in the lungs of young mice. These foci were notably absent in aged mice. However, small perivascular and peribronchial aggregates of viable mononuclear cells (arrow) were commonly found in the aged lungs. Panels C and F show young and aged lungs at 4 DPI while panel G exemplifies a lung from an aged mouse at 8 DPI. Both C and F are characterized by large foci of necrosis and lung consolidation (asterisk). At 8 DPI (G) in the aged mice there are several perivascular and peribronchial mononuclear aggregates and a few are also present at 4 DPI in moribund aged mice (F, arrow). Magnification 100X.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2990712&req=5

pone-0014088-g002: Aged mice display an altered pulmonary pathology in response to F. novicda.Young and aged mice were intransally infected with F. novicida. Lungs were harvested at various time points and H&E staining was performed to help assess the pathology associated with the course of infection. Panels A and D show mock lungs from young and aged mice, respectively. The arrow indicates perivascular mononuclear cells present in mock aged lung. Panels B and E depict the lungs of young and aged mice at 3 DPI. The asterisk is highlighting large foci of necrosis that is typical by 3 DPI in the lungs of young mice. These foci were notably absent in aged mice. However, small perivascular and peribronchial aggregates of viable mononuclear cells (arrow) were commonly found in the aged lungs. Panels C and F show young and aged lungs at 4 DPI while panel G exemplifies a lung from an aged mouse at 8 DPI. Both C and F are characterized by large foci of necrosis and lung consolidation (asterisk). At 8 DPI (G) in the aged mice there are several perivascular and peribronchial mononuclear aggregates and a few are also present at 4 DPI in moribund aged mice (F, arrow). Magnification 100X.

Mentions: In mock-infected controls and at the early time points of 6 hr and 1 day post infection the lungs of young and aged mice exhibited minor differences in terms of the cellular constituency (Fig. 2A, D and data not shown). In aged mocks, several mononuclear (monocytic) cells were present in the lungs although they seemed to be mainly present in perivascular and peribronchial areas (Fig. 2D). This cell type was generally absent from the lungs of mock young mice. Increases in the size and in some cases frequency of these perivascular infiltrates were observed at 6 hrs post infection and also at 1 DPI in aged mice (data not shown). Such aggregates were notably absent in young mice through the first two days of infection. However, by 3 DPI, the lungs of young mice began to display large foci of necrotic infiltrates and tissue destruction (Fig. 2B). Fewer and smaller foci were detected in their aged counterparts at the same time point (Fig. 2E). However, at 4 DPI (Fig. 2F) the lungs of some aged mice did begin to present with large necrotic infiltrates as seen in their young counterparts at 3 DPI (Fig. 2B). The lungs of young mice at 4 DPI showed a high level of confluence with an increasing area of necrotic tissue occluding the normal architecture of the lung (Fig. 2C, asterisk). We were not able to harvest the lungs from young mice past day 4 post infection due to the death of the animals but we were able to harvest lungs from aged mice at days 6 and 8 post infection. Surprisingly, in a subset of aged mice that survived the infection, a substantial increase in mononuclear infiltrates was evident in their lungs (Fig. 2G, arrow). However, in contrast to the infiltrates observed in moribund young or aged mice, these cellular aggregates appeared to be comprised of viable cells and were presumably protective.


Attenuated response of aged mice to respiratory Francisella novicida is characterized by reduced cell death and absence of subsequent hypercytokinemia.

Mares CA, Sharma J, Ojeda SS, Li Q, Campos JA, Morris EG, Coalson JJ, Teale JM - PLoS ONE (2010)

Aged mice display an altered pulmonary pathology in response to F. novicda.Young and aged mice were intransally infected with F. novicida. Lungs were harvested at various time points and H&E staining was performed to help assess the pathology associated with the course of infection. Panels A and D show mock lungs from young and aged mice, respectively. The arrow indicates perivascular mononuclear cells present in mock aged lung. Panels B and E depict the lungs of young and aged mice at 3 DPI. The asterisk is highlighting large foci of necrosis that is typical by 3 DPI in the lungs of young mice. These foci were notably absent in aged mice. However, small perivascular and peribronchial aggregates of viable mononuclear cells (arrow) were commonly found in the aged lungs. Panels C and F show young and aged lungs at 4 DPI while panel G exemplifies a lung from an aged mouse at 8 DPI. Both C and F are characterized by large foci of necrosis and lung consolidation (asterisk). At 8 DPI (G) in the aged mice there are several perivascular and peribronchial mononuclear aggregates and a few are also present at 4 DPI in moribund aged mice (F, arrow). Magnification 100X.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2990712&req=5

pone-0014088-g002: Aged mice display an altered pulmonary pathology in response to F. novicda.Young and aged mice were intransally infected with F. novicida. Lungs were harvested at various time points and H&E staining was performed to help assess the pathology associated with the course of infection. Panels A and D show mock lungs from young and aged mice, respectively. The arrow indicates perivascular mononuclear cells present in mock aged lung. Panels B and E depict the lungs of young and aged mice at 3 DPI. The asterisk is highlighting large foci of necrosis that is typical by 3 DPI in the lungs of young mice. These foci were notably absent in aged mice. However, small perivascular and peribronchial aggregates of viable mononuclear cells (arrow) were commonly found in the aged lungs. Panels C and F show young and aged lungs at 4 DPI while panel G exemplifies a lung from an aged mouse at 8 DPI. Both C and F are characterized by large foci of necrosis and lung consolidation (asterisk). At 8 DPI (G) in the aged mice there are several perivascular and peribronchial mononuclear aggregates and a few are also present at 4 DPI in moribund aged mice (F, arrow). Magnification 100X.
Mentions: In mock-infected controls and at the early time points of 6 hr and 1 day post infection the lungs of young and aged mice exhibited minor differences in terms of the cellular constituency (Fig. 2A, D and data not shown). In aged mocks, several mononuclear (monocytic) cells were present in the lungs although they seemed to be mainly present in perivascular and peribronchial areas (Fig. 2D). This cell type was generally absent from the lungs of mock young mice. Increases in the size and in some cases frequency of these perivascular infiltrates were observed at 6 hrs post infection and also at 1 DPI in aged mice (data not shown). Such aggregates were notably absent in young mice through the first two days of infection. However, by 3 DPI, the lungs of young mice began to display large foci of necrotic infiltrates and tissue destruction (Fig. 2B). Fewer and smaller foci were detected in their aged counterparts at the same time point (Fig. 2E). However, at 4 DPI (Fig. 2F) the lungs of some aged mice did begin to present with large necrotic infiltrates as seen in their young counterparts at 3 DPI (Fig. 2B). The lungs of young mice at 4 DPI showed a high level of confluence with an increasing area of necrotic tissue occluding the normal architecture of the lung (Fig. 2C, asterisk). We were not able to harvest the lungs from young mice past day 4 post infection due to the death of the animals but we were able to harvest lungs from aged mice at days 6 and 8 post infection. Surprisingly, in a subset of aged mice that survived the infection, a substantial increase in mononuclear infiltrates was evident in their lungs (Fig. 2G, arrow). However, in contrast to the infiltrates observed in moribund young or aged mice, these cellular aggregates appeared to be comprised of viable cells and were presumably protective.

Bottom Line: Age associated attenuations of various immune parameters, involved with both innate and adaptive responses are collectively known as immune senescence.These changes are likely to be involved with differences in host susceptibility to disease between young and aged individuals.In addition, the small cohort of aged survivors did not progress to a severe sepsis syndrome with hypercytokinemia, as did all of the young adult mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.

ABSTRACT

Background: Pneumonia and pulmonary infections are major causes of mortality among the growing elderly population. Age associated attenuations of various immune parameters, involved with both innate and adaptive responses are collectively known as immune senescence. These changes are likely to be involved with differences in host susceptibility to disease between young and aged individuals.

Methodology/principal findings: The objective of this study was to assess potential age related differences in the pulmonary host response in mice to the Gram-negative respiratory pathogen, Francisella novicida. We intranasally infected mice with F. novicida and compared various immune and pathological parameters of the pulmonary host response in both young and aged mice.

Conclusions/significance: We observed that 20% of aged mice were able to survive an intranasal challenge with F. novicida while all of their younger cohorts died consistently within 4 to 6 days post infection. Further experiments revealed that all of the aged mice tested were initially able to control bacterial replication in the lungs as well as at distal sites of replication compared with young mice. In addition, the small cohort of aged survivors did not progress to a severe sepsis syndrome with hypercytokinemia, as did all of the young adult mice. Finally, a lack of widespread cell death in potential aged survivors coupled with a difference in cell types recruited to sites of infection within the lung confirmed an altered host response to Francisella in aged mice.

Show MeSH
Related in: MedlinePlus