Neutrophils and eosinophils are granulocytes that have very distinct functions. Neutrophils are first responders to external threats, and they use different mechanisms to control pathogens. Phagocytosis, reactive oxygen species, and neutrophil extracellular traps (NETs) are some of the mechanisms that neutrophils utilize to fight pathogens. Although there is some controversy as to whether NETs are in fact beneficial or detrimental to the host, it mainly depends on the biological context. NETs can contribute to disease pathogenesis in certain types of diseases, while they are also undeniably critical components of the innate immune response. On the contrary, the role of eosinophils during host immune responses remains to be better elucidated. Eosinophils play an important role during helminthic infections and allergic responses. Eosinophils can function as effector cells in viral respiratory infections, gut bacterial infections, and as modulators of immune responses by driving the balance between Th1 and Th2 responses. In particular, eosinophils have biological activities that appear to be quite similar to those of neutrophils. Both possess bactericidal activity, can activate proinflammatory responses, can modulate adaptive immune responses, can form extracellular traps, and can be beneficial or detrimental to the host according to the underlying pathology. In this review we compare these two cell types with a focus on highlighting their numerous similarities related to extracellular traps.

A common feature of pathogens is their ability to suppress host immune responses. Understanding the molecular mechanisms and the common pathways that bacteria utilize to block host immune signaling cascade might provide novel avenues for vaccine and therapeutic development. Preventable infectious diseases remain one of the major causes of morbidity and mortality worldwide and the current rise in antibiotic resistance is increasing this burden. Bordetella spp. are respiratory pathogens that cause the long-term illness known as whoop-ing cough. Bordetella infections cause over 150,000 deaths each year, despite a vaccine be-ing available. In our studies, we used the mouse pathogen B. bronchiseptica to investigate the pneumonic stage of disease, which very well mimics the fatal disease caused by B. pertussis. In our previous work we discovered a B. bronchiseptica mutant, RB50DbtrS, that clears rapidly from the lungs of mice and generates protective immunity that lasts for at least 15 months post-challenge. Combining the mouse immunological tools and both bacteria, the wildtype RB50 and mutant RB50DbtrS, which persists for up to 56 days and clears in 14-21 days, respectively, we investigated the mechanisms by which the wildtype B. bronchiseptica blocks host immune response to cause long term lung infection. Previous research indicated eosinophils as critical for rapid clearance of the mutant bacteria from the lungs. In vitro assays with eosinophils demonstrated that the RB50DbtrS mutant strain promotes the secretion of pro-inflammatory signals. In contrast, infection of eosinophils with RB50 promoted the se-cretion of anti-inflammatory signals such as IL1RA. Interestingly, IL1RA was also increased in the lungs of mice infected with the wildtype but not with the mutant RB50 strain. Infection with RB50DbscN, which lacks a functional type 3 secretion system (T3SS), was sufficient to prevent IL1RA induction suggesting that the bacterial effector responsible for IL1RA upregula-tion is a substrate of the T3SS. Supplementation with IL1RA after infection with RB50 or RB50DbtrS resulted in increased lung bacterial burden for both bacterial strains. However, more rapid clearance of RB50 was observed after infection of mice in which IL1RA was knocked out. Furthermore, anti-IL1RA antibody treatment promoted rapid clearance of not only RB50 but also the human pathogens B. pertussis and B. parapertussis. This suggests that IL1RA may be a promising therapeutic target to treat severe cases of whooping cough. Overall, this work demonstrates that Bordetella spp. induces IL1RA expression to promote persistence using the T3SS. Since other bacteria have also been shown to target IL1RA, this may be a conserved bacterial mechanism to promote host-immune suppression.