Limits...
Border Patrol Gone Awry: Lung NKT Cell Activation by Francisella tularensis Exacerbates Tularemia-Like Disease.

Hill TM, Gilchuk P, Cicek BB, Osina MA, Boyd KL, Durrant DM, Metzger DW, Khanna KM, Joyce S - PLoS Pathog. (2015)

Bottom Line: Here we show for the first time that respiratory infection with Francisella tularensis live vaccine strain resulted in rapid accumulation of NKT cells within the lung interstitium.Consistent with these results, NKT cell-deficient mice showed reduced inflammatory cytokine and chemokine response yet they survived the infection better than their wild type counterparts.Strikingly, NKT cell-deficient mice had increased lymphocytic infiltration in the lungs that organized into tertiary lymphoid structures resembling induced bronchus-associated lymphoid tissue (iBALT) at the peak of infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.

ABSTRACT
The respiratory mucosa is a major site for pathogen invasion and, hence, a site requiring constant immune surveillance. The type I, semi-invariant natural killer T (NKT) cells are enriched within the lung vasculature. Despite optimal positioning, the role of NKT cells in respiratory infectious diseases remains poorly understood. Hence, we assessed their function in a murine model of pulmonary tularemia--because tularemia is a sepsis-like proinflammatory disease and NKT cells are known to control the cellular and humoral responses underlying sepsis. Here we show for the first time that respiratory infection with Francisella tularensis live vaccine strain resulted in rapid accumulation of NKT cells within the lung interstitium. Activated NKT cells produced interferon-γ and promoted both local and systemic proinflammatory responses. Consistent with these results, NKT cell-deficient mice showed reduced inflammatory cytokine and chemokine response yet they survived the infection better than their wild type counterparts. Strikingly, NKT cell-deficient mice had increased lymphocytic infiltration in the lungs that organized into tertiary lymphoid structures resembling induced bronchus-associated lymphoid tissue (iBALT) at the peak of infection. Thus, NKT cell activation by F. tularensis infection hampers iBALT formation and promotes a systemic proinflammatory response, which exacerbates severe pulmonary tularemia-like disease in mice.

No MeSH data available.


Related in: MedlinePlus

Reduced susceptibility of CD1d-/- mice is not dependent on strain background.(A) Groups of 6–8 week-old BALB/c or CD1d-/- mice were infected intranasally with different doses of LVS as indicated and monitored for survival (n = 8 mice/group) (B) BALB/c or CD1d-/- mice were infected intranasally with 6 cfu Schu S4 and monitored for survival (n = 8 mice/group).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4465904&req=5

ppat.1004975.g009: Reduced susceptibility of CD1d-/- mice is not dependent on strain background.(A) Groups of 6–8 week-old BALB/c or CD1d-/- mice were infected intranasally with different doses of LVS as indicated and monitored for survival (n = 8 mice/group) (B) BALB/c or CD1d-/- mice were infected intranasally with 6 cfu Schu S4 and monitored for survival (n = 8 mice/group).

Mentions: Given the observed differences in susceptibility among various mouse strains [61–64], we next ascertained whether CD1d-/- mice in the BALB/c background would exhibit the same phenotype. Consistent with the results in C57BL6 background, we found that CD1d-/- mice were less susceptible to LVS infection in the BALB/c background as well (Fig 9A). As observed with C57BL6 mice, higher doses caused severe disease in both groups, although death was slightly delayed in CD1d-deficient mice.


Border Patrol Gone Awry: Lung NKT Cell Activation by Francisella tularensis Exacerbates Tularemia-Like Disease.

Hill TM, Gilchuk P, Cicek BB, Osina MA, Boyd KL, Durrant DM, Metzger DW, Khanna KM, Joyce S - PLoS Pathog. (2015)

Reduced susceptibility of CD1d-/- mice is not dependent on strain background.(A) Groups of 6–8 week-old BALB/c or CD1d-/- mice were infected intranasally with different doses of LVS as indicated and monitored for survival (n = 8 mice/group) (B) BALB/c or CD1d-/- mice were infected intranasally with 6 cfu Schu S4 and monitored for survival (n = 8 mice/group).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4465904&req=5

ppat.1004975.g009: Reduced susceptibility of CD1d-/- mice is not dependent on strain background.(A) Groups of 6–8 week-old BALB/c or CD1d-/- mice were infected intranasally with different doses of LVS as indicated and monitored for survival (n = 8 mice/group) (B) BALB/c or CD1d-/- mice were infected intranasally with 6 cfu Schu S4 and monitored for survival (n = 8 mice/group).
Mentions: Given the observed differences in susceptibility among various mouse strains [61–64], we next ascertained whether CD1d-/- mice in the BALB/c background would exhibit the same phenotype. Consistent with the results in C57BL6 background, we found that CD1d-/- mice were less susceptible to LVS infection in the BALB/c background as well (Fig 9A). As observed with C57BL6 mice, higher doses caused severe disease in both groups, although death was slightly delayed in CD1d-deficient mice.

Bottom Line: Here we show for the first time that respiratory infection with Francisella tularensis live vaccine strain resulted in rapid accumulation of NKT cells within the lung interstitium.Consistent with these results, NKT cell-deficient mice showed reduced inflammatory cytokine and chemokine response yet they survived the infection better than their wild type counterparts.Strikingly, NKT cell-deficient mice had increased lymphocytic infiltration in the lungs that organized into tertiary lymphoid structures resembling induced bronchus-associated lymphoid tissue (iBALT) at the peak of infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.

ABSTRACT
The respiratory mucosa is a major site for pathogen invasion and, hence, a site requiring constant immune surveillance. The type I, semi-invariant natural killer T (NKT) cells are enriched within the lung vasculature. Despite optimal positioning, the role of NKT cells in respiratory infectious diseases remains poorly understood. Hence, we assessed their function in a murine model of pulmonary tularemia--because tularemia is a sepsis-like proinflammatory disease and NKT cells are known to control the cellular and humoral responses underlying sepsis. Here we show for the first time that respiratory infection with Francisella tularensis live vaccine strain resulted in rapid accumulation of NKT cells within the lung interstitium. Activated NKT cells produced interferon-γ and promoted both local and systemic proinflammatory responses. Consistent with these results, NKT cell-deficient mice showed reduced inflammatory cytokine and chemokine response yet they survived the infection better than their wild type counterparts. Strikingly, NKT cell-deficient mice had increased lymphocytic infiltration in the lungs that organized into tertiary lymphoid structures resembling induced bronchus-associated lymphoid tissue (iBALT) at the peak of infection. Thus, NKT cell activation by F. tularensis infection hampers iBALT formation and promotes a systemic proinflammatory response, which exacerbates severe pulmonary tularemia-like disease in mice.

No MeSH data available.


Related in: MedlinePlus