Effect of Genetic Background on the Response to Bacterial Sinusitis in Mice

Abstract

To study the importance of ongoing allergen exposure and T H 1/T H 2 genetic background in augmented bacterial and inflammatory responses in allergic and infected mice.Design: BALB/c and C57BL/6 mice were made allergic to ovalbumin. After 1 day of intranasal allergen exposure, they were inoculated intranasally with Streptococcus pneumoniae. The numbers of bacteria and inflammatory cells in the sinuses were determined, and nasal responsiveness to histamine was assessed.Results: Infected BALB/c and C57BL/6 mice that received ongoing ovalbumin challenge following intraperitoneal sensitization showed significantly greater bacterial load and phagocyte level compared with the infected-only mice. Differences were diminished after the allergen challenge was stopped. Allergic and infected C57BL/6 mice showed fewer bacteria and phagocytes compared with the allergic and infected BALB/c mice. Surprisingly, in contrast to the nonallergenic C57BL/6 mice, the infected BALB/c mice showed a larger number of bacteria 28 days after infection.Conclusions: Ongoing allergic reaction augments bacterial load in both BALB/c and C57BL/6 mice and induces nasal hyperreactivity to histamine. Allergic and infected C57BL/6 mice show less allergic inflammation and bacterial load compared with allergic and infected BALB/c mice. Stopping allergen exposure reduces the response. Infected BALB/c mice, which favor a T H 2 response, were less able to clear infection than C57BL/6 mice, which favor a T H 1 response. Inflammation and bacterial load are affected by genetic background of mice and ongoing allergen stimulation.

Th2 Cytokines associated with Chronic Rhinosinusitis with Polyps Down-Regulate the Antimicrobial Immune Function of Human Sinonasal Epithelial Cells

“…In both cases, airway Th2 inflammation leads to decreased expression of innate immune genes and reduced capacity to clear experimentally induced infection. 18,19 Taken together, these studies strongly support the validity of the in vitro findings with HSNECs that we have described.…”

“…18 Further evidence of a down-regulation of innate immunity in Th2 nasal inflammation is provided by a study by Kirtsreesakul et al examining clearing of Streptococcus pneumoniae infection in allergic mice. 19 It was found that nasal allergen-sensitized BALB/c mice (in which a Th2 inflammatory response is favored) were less able to clear infection than C57BL/6 mice (which favor a Th1 response). Our previous observation that TLR and immune effector genes are down-regulated in recalcitrant CRSwNP patients is consistent with a similar suppression of epithelial innate immune function by Th2 cytokines within the sinonasal mucosa.…”

Deprived TLR9 Expression in Apparently Healthy Nasal Mucosa Might Trigger Polyp-Growth in Chronic Rhinosinusitis Patients

“…This is reflected in B cells and pDCs showing increased expression of costimulatory molecules, upregulation of the chemokine receptor, CCR7, and secretion of Th1-promoting chemokines as well as cytokines, such as MIP-1β and IFN-γ–inducible protein-10 [40]. Although no mouse model currently exists for CRSwNP, mice with upper and lower allergic Th2 inflammation exhibit a decreased expression of innate immune genes and reduced capacity to clear infection [41], [42]. It is important to recognize that, in contrast to what was seen in epithelial cells from turbinate tissue, no cytokine reduction was found in the polyp tissue as a result of the CpG stimulation.…”

Environmental and Genetic Contributions to Indicators of Oral Malodor in Twins

“…Similarly, the presence of sinus infections indicates a breakdown in mucosal defenses against bacteria and viruses, which may also be mediated by genetic factors. Indeed, animal studies suggest that genetic background is involved in responses to bacterial sinusitis (Kirtsreesakul et al, 2006). …”