Abstract
Polymorphonuclear neutrophils (PMNs) are the first line of defense against microbial pathogens. In addition to their role in innate immunity, PMNs may also regulate events related to adaptive immunity. To investigate the influence of PMNs in the immune response during chronic bacterial infections, we explored the course of brucellosis in antibody PMN-depleted C57BL/6 mice and in neutropenic mutant Genista mouse model. We demonstrate that at later times of infection, Brucella abortus is killed more efficiently in the absence of PMNs than in their presence. The higher bacterial removal was concomitant to the: i) comparatively reduced spleen swelling; ii) augmented infiltration of epithelioid histiocytes corresponding to macrophages/dendritic cells (DCs); iii) higher recruitment of monocytes and monocyte/DCs phenotype; iv) significant activation of B and T lymphocytes, and v) increased levels of INF-γ and negligible levels of IL4 indicating a balance of Th1 over Th2 response. These results reveal that PMNs have an unexpected influence in dampening the immune response against intracellular Brucella infection and strengthen the notion that PMNs actively participate in regulatory circuits shaping both innate and adaptive immunity.
Highlights
Neutrophils are the first line of defense against microbial pathogens
A mouse strain named Genista, in which the defect is the absence of polymorphonuclear leukocytes (PMNs) has been developed; making possible to explore the role of PMNs during adaptive immunity in chronic infections
We found that the absence PMNs is non-lethal and favors Brucella elimination at later times of infection, a phenomenon that correlates with the balance of Th1 over Th2 response
Summary
Neutrophils are the first line of defense against microbial pathogens. Upon bacterial infection, these polymorphonuclear leukocytes (PMNs) become activated and are rapidly recruited to the infection site where they can efficiently constrain and kill microbes via phagocytosis, extracellular release of granule contents, cytokine secretion, and the formation of neutrophil extracellular traps [1]. In addition to playing a primary role during the course of innate immunity against acute bacterial infections, PMNs may influence adaptive immunity [2,3,4,5]. In addition to their direct antimicrobial activity, mature neutrophils seem to be endowed with unsuspected immunoregulatory functions that seem to be conserved across species [9]
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