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The Podophage PM16 Enhances the Humoral Immune Response Against Proteus mirabilis
Lina Al Allaf1, Anton V Chechushkov1, Vera V Morozova1
1Laboratory of Molecular Microbiology, Institute of Chemical Biology and Fundamental Medicine Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.
Abstract:
Considering the therapeutic potential of the Proteus mirabilis PM16 podophage, the interaction between PM16, its host strain, and the mouse immune system was investigated. We evaluated how pre-existing humoral immunity to PM16 influences the immune response against P. mirabilis and the neutralization of the phage itself. Balb/c mice were divided into three groups and immunized two times with (1) 0.9% NaCl, (2) adjuvants, or (3) a mixture of PM16 and an adjuvant. Then, each group was subdivided into three subgroups: mock infection, infection with P. mirabilis, and infection with P. mirabilis followed by model phage therapy with PM16. The obtained results demonstrated that pre-immunization with PM16 enhanced the anti-P. mirabilis IgG antibody response upon bacterial challenge, indicating that the phage potentiates antibacterial immunity. In addition, pre-immunization elicited a significant anti-PM16 antibody response that resulted in in vitro neutralization of phage lytic activity. However, phage-neutralizing antibodies neither decreased the efficacy of phage therapy nor influenced bacteria-specific immune response. Thus, while PM16 can boost the host's immune response against its bacterial host, the resulting humoral immunity also drives phage clearance through both direct and bacteria-mediated neutralization pathways, revealing a complex immunopharmacological relationship central to phage therapy.
Insights
Pre-immunization with the Proteus mirabilis PM16 phage enhances antibacterial immunity but also triggers phage-neutralizing antibodies. These antibodies do not impede phage therapy efficacy, revealing a complex phage-host immune interaction.
Area of Science:
- Microbiology
- Immunology
- Bacteriophage Therapy
Background:
- Proteus mirabilis is an opportunistic pathogen.
- Bacteriophage therapy offers an alternative to antibiotics.
- Understanding phage-host immune interactions is crucial for phage therapy efficacy.
Purpose of the Study:
- To investigate the immunomodulatory effects of the PM16 podophage on the host immune system.
- To evaluate how pre-existing humoral immunity to PM16 affects the immune response against P. mirabilis.
- To assess the impact of anti-PM16 antibodies on phage neutralization and therapy effectiveness.
Main Methods:
- Balb/c mice were immunized with saline, adjuvant, or PM16 plus adjuvant.
- Mice were subsequently challenged with P. mirabilis, with or without phage therapy.
- Humoral immune responses (IgG antibodies) and phage neutralization were measured.
Main Results:
- PM16 pre-immunization enhanced anti-P. mirabilis IgG antibody response, potentiating antibacterial immunity.
- Pre-immunization induced anti-PM16 antibodies, neutralizing phage lytic activity in vitro.
- Phage-neutralizing antibodies did not reduce phage therapy efficacy or alter the bacteria-specific immune response.
Conclusions:
- The PM16 phage can augment host immune responses against P. mirabilis.
- Humoral immunity against the phage leads to its clearance via neutralization pathways.
- A complex immunopharmacological interplay exists between phage, host bacteria, and the host immune system, critical for phage therapy.
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