Bordetella pertussis Infection Exacerbates Influenza Virus Infection through Pertussis Toxin-Mediated Suppression of Innate Immunity

Pertussis (whooping cough) is frequently complicated by concomitant infections with respiratory viruses. Here we report the effect of Bordetella pertussis infection on subsequent influenza virus (PR8) infection in mouse models and the role of pertussis toxin (PT) in this effect. BALB/c mice infected with a wild-type strain of B. pertussis (WT) and subsequently (up to 14 days later) infected with PR8 had significantly increased pulmonary viral titers, lung pathology and mortality compared to mice similarly infected with a PT-deficient mutant strain (ΔPT) and PR8. Substitution of WT infection by intranasal treatment with purified active PT was sufficient to replicate the exacerbating effects on PR8 infection in BALB/c and C57/BL6 mice, but the effects of PT were lost when toxin was administered 24 h after virus inoculation. PT had no effect on virus titers in primary cultures of murine tracheal epithelial cells (mTECs) in vitro, suggesting the toxin targets an early immune response to increase viral titers in the mouse model. However, type I interferon responses were not affected by PT. Whole genome microarray analysis of gene expression in lung tissue from PT-treated and control PR8-infected mice at 12 and 36 h post-virus inoculation revealed that PT treatment suppressed numerous genes associated with communication between innate and adaptive immune responses. In mice depleted of alveolar macrophages, increase of pulmonary viral titers by PT treatment was lost. PT also suppressed levels of IL-1β, IL-12, IFN-γ, IL-6, KC, MCP-1 and TNF-α in the airways after PR8 infection. Furthermore PT treatment inhibited early recruitment of neutrophils and NK cells to the airways. Together these findings demonstrate that infection with B. pertussis through PT activity predisposes the host to exacerbated influenza infection by countering protective innate immune responses that control virus titers

Diphtherial Toxoid Purified by Absorption

In spite of numerous investigations conducted over a period of many years, detoxified crude bacterial filtrates are still commonly used in prophylaxis against diphtheria. Many attempts have been made to purify diphtherial toxin and toxoid, including experiments in absorption with calcium phosphate, but much remains to be learned. More information is required concerning antigenicity, reaction upon injection, and methods of manufacturing purified toxoid. At the present time, the crude fluid (bacterial filtrate) and alum-precipitated toxoids are used mainly for the immunization of children who can tolerate them better than adults. Crude toxoid prepared by detoxification of bacterial filtrates with formalin, in addition to proteins of true exotoxin, contains somatic antigens, i.e., soluble substances of proteinic nature that form precipitins with antibacterial serum. The biological significance of these substances and methods of their separation from the toxin have been discussed in our earlier publication (Parfentjev et al., 1942). It was shown that under controlled conditions selective absorption o

The immunological response to bacterial antigen and its effect on mouse tumor. Abstr.

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