Research shows that bacteria use hydrogen peroxide to weaken the immune system and cause pneumonia.
This according to a study at Umeå University and Stockholm University, Sweden.
Hydrogen peroxide is also known as a bleaching agent that is used to whiten teeth or hair, as a stain remover, as well as for cleaning surfaces and disinfecting wounds.
“By using hydrogen peroxide to defeat the immune system, you could say that the bacteria are fighting fire with fire.
The body itself also produces hydrogen peroxide as a defense against the bacteria.
Therefore, it was surprising to see that many types of bacteria actually use the same substance to overcome the body’s defenses,” says Nelson Gekara, research leader.
Saskia Erttmann and Nelson Gekara mainly focused their studies on Streptococcus pneumoniae.
This bacterium, often called pneumococcus, is the most common bacterium causing pneumonia but can also cause, among other illnesses, meningitis or severe sepsis.
In addition, this bacterium can pave the way for other microbes to attack.
This makes the bacterium among the most deadly in the world.
Many people harbor the bacterium in the upper respiratory tract as a part of their normal flora without falling ill or even knowing about it.
It is therefore important to understand how pneumococci affect the immune system.
The ultimate goal of any invading microbe is to reside peacefully in the body without evoking a strong inflammatory reaction.
The researchers have found that pneumococcus and other bacteria accomplish this by targeting a key component of the immune system – the inflammasomes, protein complexes, which, upon recognizing foreign molecules, initiate reactions to kill microbes and to clear diseased cells.
The researchers found that bacteria such as pneumococci release large quantities of hydrogen peroxide, and that this causes inactivation of inflammasomes, thereby weakening the immune system.
In mice models, the researchers observed that bacteria manipulated to produce less hydrogen peroxide were unable to inactivate inflammasomes and therefore elicited a faster inflammatory response that effectively cleared the bacteria from mouse lungs.
The researchers also found that by inoculating the mice with a special enzyme, catalase, which breaks down hydrogen peroxide, the inflammation and inflammatory symptoms increased, leading to faster elimination of pneumococci from the lung.
“Inflammation often has negative connotations. However, for the body, inflammation is an important process in the immune system’s defense against attacking microbes.
Most microbes produce hydrogen peroxide to varying degrees.
Our studies demonstrate that hydrogen peroxide is an inhibitor of an important component of the inflammatory machinery, suggesting that the mechanism we have uncovered is a common strategy employed by many microbes to thrive within us,” says Saskia Erttmann, first author in the study and former member of Nelson Gekara’s research group.
“One of the best known substances with the ability to neutralize hydrogen peroxide and that could hence boost anti-bacterial immunity are vitamins such as vitamin C, found in fruits. Perhaps the old adage ‘an apple a day keeps the doctor away’ is not off the mark,” adds Nelson Gekara.
Hydrogen peroxide (H2O2) is a ubiquitous metabolic byproduct of aerobic unicellular and multicellular organisms1,2,3,4 that plays a major role in determining the outcome of host-microbial interactions5.
Thus far, studies have focused on endogenous H2O2 produced by immune cells and its role in killing microbes or driving inflammatory processes1,5,6,7,8.
However, H2O2 generation is not a preserve of eukaryotic host cells—many microbes do produce H2O21,4. How H2O2 produced by microbes affect the dynamic of host-microbial interactions, and in particular the ability of immune cells to respond to microbes, remains unknown.
Accumulation of H2O2 to high levels can be toxic to both the host and the microbe. To mitigate these undesired effects, most organisms are equipped with enzymes such as catalase to neutralize H2O22.
However, some bacterial species lack catalase. One well-known example is S. pneumoniae. Consequently, a major hallmark of S. pneumoniae infection is massive production of H2O2, which can accumulate up to millimolars in in vitro cultures9,10.
Considering that up to ∼108 cfu/mL of S. pneumoniaehas been documented in infected lungs11, it is likely that the concentration of H2O2 in vivo, especially at the infection foci, is equally high hence can be detected in the breath of patients12.
While H2O2 production is responsible for autolysis of bacteria at stationary phase, generally, S. pneumoniae is highly resistant to H2O2 via mechanisms not fully understood13,14.
This resistance allows S. pneumoniae not only to outcompete other bacteria from the host niche but likely also to withstand H2O2 produced by immune cells. But how H2O2 produced by bacteria afffects the anti-microbial response of immune cells is unresolved.
Microbes—especially those that have established a long-standing co-existence with their hosts have evolved diverse mechanisms to mitigate anti-microbial innate immune defenses13,14,15. S. pneumoniae is a habitant of the upper respiratory tract and the most common causative agent of community-acquired pneumonia, a leading cause of death worldwide16,17.
Infections with S. pneumoniae possibly also promote invasion of the airways by other pathogens16,17.
How S. pneumoniae overcomes the innate immune system to persist in the host has remained unclear. Here we reveal that S. pneumoniaeactively inhibits inflammasomes—key components of the innate immune system.
This contributes to its ability to colonize the host but also renders immune cells unresponsive to other inflammasome stimuli during co-infections. We demonstrate that this phenomenon is due to S. pneumoniae-generated H2O2, which causes oxidative inactivation of inflammasomes.
Further, we show that other H2O2-producing bacteria such as Streptococcus oralis, an oral commensal, similarly block inflammasomes.
This study uncovers an unanticipated role of microbial H2O2 in innate immune suppression, and how this promotes host colonization by microbes.
More information: Saskia F. Erttmann et al, Hydrogen peroxide release by bacteria suppresses inflammasome-dependent innate immunity, Nature Communications (2019). DOI: 10.1038/s41467-019-11169-x
Journal information: Nature Communications
Provided by Umea University
